In the aftermath of their journey to another planet, Director Phil Coulson and the rest of the team were driven more than ever to put an end to the HYDRA organization. Little did they know that they were up against the deadliest threat they've ever faced – an extremely powerful Inhuman, Hive, who was transported back from Maveth in the body of their worst enemy, Grant Ward. The team was able to thwart and kill Hive and take down HYDRA, but they are all still mourning the death of fellow agent and Inhuman, Lincoln Campbell.
In light of the Sokovia Accords, and with HYDRA obliterated, S.H.I.E.L.D. has been legitimized again and no longer needs to operate in the shadows. Since the world presumes that Coulson is dead, the organization needed a new Director to be the face of the organization. Coulson finds himself back in the role as an agent and teamed with Mack, and together they are tasked with tracking down and confirming the presence of Enhanced people, aka Inhumans. They have been trying to track down and capture Daisy, aka Quake, who has gone rogue in an attempt to atone for sins from the past. But with the world believing that Daisy is a dangerous outlaw who has taken down banks and bridges, the new Director has no qualms about taking her down for good. Agent May is tasked with training specialist strike teams, and Fitz and Simmons have taken a big step forward in their relationship. But with Simmons' new promotion as Special Advisor to the Director in Science and Technology, Fitz, as well as her former team members, finds it hard to confide in or trust her since she's now the Director's confidant.
Robbie Reyes will roar into the lives of Agent Coulson and the team as a junkyard mechanic who can turn on a dime into the terrifying Ghost Rider. Will Robbie be a friend or foe to S.H.I.E.L.D. – as well as the world, itself? Meanwhile, Fitz discovers that socially awkward genius and friend Dr. Radcliffe has started putting the finishing touches on a new, secret invention.
On the heels of their encounter with Ghost Rider, their strangest phenomenon yet, the Agents of S.H.I.E.L.D. suddenly find themselves up against a myriad of new and ongoing threats: The anti-Inhuman Watchdogs are gaining political influence with Senator Nadeer, and uniting behind a mysterious benefactor. Meanwhile, unbeknownst to the team, Aida has kidnapped Agent May and replaced her with a Life Model Decoy. Aida's evil plans for May and the team remain a mystery.
On the heels of their encounter with Ghost Rider and battling the Watchdogs to their highest ranks, the Agents of S.H.I.E.L.D. find themselves in their most mind-bending mission yet. The heroes have been plugged into a virtual reality known as "The Framework," created by Dr. Radcliffe and Fitz. They awake to find themselves in an unrecognizable world – a world in which Hydra reigns supreme. What will become of the team as they make their way through this strange new landscape? What friends and foes will they face? And ultimately, will they ever escape and return to their real lives?
In 2012, Lucy Bauer and her husband Joseph Bauer find a book called the Darkhold. They find it has magical properties and use it for a project along with others and Eli Morrow. However, as time went on, Bauer notices Morrow's greed for power. The project goes wrong and turns them all except for Joseph and Morrow into ghosts. Joseph is knocked into a coma and Morrow is sent to jail. On that night, Morrow's nephews, Robbie Reyes and Gabe Reyes drive their uncle's car when they are ambushed by the Fifth Street Locos, who mistake them for Morrow. Robbie is shot into the air and pleads to anyone to spare his brother. He hits the road and dies. Suddenly, the Ghost Rider arrives and imbues Robbie with the Spirit of Vengeance. Reviving Robbie and saving Gabe but leaving him paralyzed. Robbie is forced to kill anyone that the Rider deems deserved.
In present say, following the defeat of Hive, S.H.I.E.L.D. Agent Daisy Johnson is consumed with guilt over the death of her fellow agent and lover, Lincoln Campbell. To help cope with her grief, she has left S.H.I.E.L.D., effectively going rogue. Taking on the alias "Quake", Johnson begins engaging in vigilante activity, directly opposing the actions of the anti-Inhuman mercenary organization, the Watchdogs. During her latest engagement, she runs afoul a group of gangsters in Los Angeles. The confrontation is suddenly interrupted by the unexpected arrival of a second vigilante with fire-based abilities, who slaughters the gangsters in cold blood. Through investigation, Johnson comes to learn that the vigilante is Robbie Reyes, a local mechanic. She befriends the vigilante. Reyes' actions also gain the attention of S.H.I.E.L.D.
Over the months, Leo Fitz has developed a good relationship with fellow scientist Holden Radcliffe as well as grown his loving relationship with Jemma Simmons. They have also been working on a virtual world called the Framework. Radcliffe feels good enough about Fitz to show him his project, Artificially Intelligent Digital Assistance or Aida for short. Fitz worries about the Life-Model Decoy and how it is illegal because of the Sokovia Accords. Additionally, the new director Jeffrey Mace has had a tight leash on Simmons as well as a big enforcer of the Accords.
Lucy Bauer escapes from her box and haunts many people including Melinda May. May starts experiencing frightening hallucinations causing her to go crazy. May begins to attack the STRIKE team and is stopped by the director, who reveals his Inhuman powers of strength and durability to them.
Alphonso Mackenzie and Leo Fitz go to stop Bauer and encounter Ghost Rider. The Rider is the only person that can touch the Ghost and is able to kill another ghost. They also encounter Johnson and help her heal. Mack finds out that Yo-Yo Rodriguez has been regularly supplying Johnson with pills to counter injuries from the overuse of her powers. Fitz angrily tells Johnson that she betrayed them. Meanwhile, Rodriguez leaves for Miami to attend a party with her friends. Robbie Reyes introduces Johnson to his brother, Gabe Reyes. Gabe recognizes Johnson as Quake and tells her to stay away from his brother, she leaves and Robbie comes home to find her gone.
The Watchdogs set off an EMP in major cities across the United States of America. It is blamed on the Inhumans. The worsening May is brought to Radcliffe's home to prevent any death. Radcliffe has the idea of killing May then reviving her so that her brain resets. Simmons decides to comply because she would be dead anyway. While May's heart stops, an EMP sets off the power making it impossible to revive May. Radcliffe decides to reveal Aida is order to use her power source to revive her. It works and May is cured, but Simmons now knows about Aida. The team stops the EMP and saves the electricity. Back at S.H.I.E.L.D. Headquarters, Director Mace reveals S.H.I.E.L.D. to the world. Now alone, Johnson tricks Simmons into coming to an abandoned apartment thinking it is for sale. Simmons helps the wounded Johnson and she asks Simmons to help her find wanted Inhumans and save them. On the list is JT James.
Meanwhile, Coulson visits Eli Morrow in jail to talk to him about the incident that he was involved in that turned Bauer and others into ghosts. When leaving Robbie shows up to talk to his Uncle Eli, Mack recognizes him and they take him in. Robbie decides to work with S.H.I.E.L.D. and now Johnson to stop the ghosts. They go to James' firework shop and find that he is a Watchdog and the man who has leaked the Inhuman's locations. He is stopped after a fight with Ghost Rider. Lucy Bauer finds the Darkhold, but is unable to read it. Robbie brings Gabe aboard the Quinjet. Mace comes aboard and looks around, knowing that Quake is there. Quake and the Reyes brothers hide in the containment module under the Quinjet while Robbie tells Gabe the truth about him as Ghost Rider and the night of the accident. They are then found and Ghost Rider lashes out of Robbie because he doesn't want to get arrested. He and the Inhuman Director fight and Mace is almost killed before Gabe yells for his brother to stop.
The team goes to confront Bauer and finds that Morrow has broken out and is now working with Bauer. They enter the facility and Reyes kills Bauer. They find that Morrow has used the Darkhold and a machine to give himself the power to generate carbon by taking it from other dimensions. He also reveals he was the one to set off the explosion that turned everyone into ghosts. The machine then explodes and sets off a shock wave that causes Fitz, Coulson, and Reyes to seemingly disappear into thin air.
Fitz, Coulson, and Reyes find that they are invisible to the eye and stuck in between dimensions. The team thinks that the trio has died and mourn the loss, but May doesn't believe it and thinks the Darkhold can get them back. Meanwhile, the trio has followed the team this whole time, but Reyes suddenly feels cold, saying that the Ghost Rider is mad and wants out. The Spirit of Vengeance then goes out of Reyes and into Mackenzie making him the new Ghost Rider. Mackenzie drives his motorcycle out of the Quinjet without a word and Johnson follows him and Reyes' car. Reyes manages to get into the car as well despite Johnson not being able to see him. Reyes finds Mackenzie and tells the Rider he will settle any score the Rider wants. The Spirit then goes back into Reyes. Meanwhile, May suggests that Aida reads the Darkhold so it doesn't corrupt the mind of a human. Aida reads it and creates a portal to get Fitz and Coulson back, it works and they are saved. Mack is reminded of something that makes him upset. He holds a note in his hand while crying. The note says "Hope 4/18/06" signifying his daughter who died shortly after birth. Reyes then goes through the portal and asks Mack if he wants ti help him settle his last score.
Meanwhile, Director Mace sends Simmons to Senator Ellen Nadeer's house. Nadeer is an avid Inhuman hater but Mace thinks it's good for publicity. Simmons helps her brother, Vijay Nadeer, who seems to be stuck in a Terrigenesis cocoon. Now advanced from the Darkhold, Aida begins to assemble a brain to use for unknown reasons.
The team tracks down Morrow and try to stop him. Morrow is confronted by Reyes, Morrow sends a carbon spike into his nephew. Reyes says that the Devil is coming to which Morrow sends a second spike into him and leaves. After a long battle, Ghost Rider has Morrow trapped in an Inter-Dimensional Gate and Coulson throws him a chain to get out. Reyes drops the chain and decides to burn Morrow alive and get sent through the gate, seemingly never coming back. Overwhelmed, Johnson runs out and Quakes the ground, sending her into the air so she can catch a breath. When coming down, she gets surrounded by reporters, Mace comes in saying the Johnson has been undercover for S.H.I.E.L.D. and explains her illegal activities.
At the headquarters, Rodriguez and Mackenzie finally move forward in their relationship. At the Radcliffe Residence, Agent Nathan B. Nathanson goes in to check on Radcliffe as they have made a deal that LMD's can remain a project under supervision. He looks in a closet to find Melinda May unconscious, he is then killed by Aida, who snaps his neck.
S.H.I.E.L.D. moves in on the Radcliffe Residence to reset Aida's memory per the agreement. They are met by a hostile Aida who attacks them and escapes. At the S.H.I.E.L.D. Headquarters, they look for Aida. She is found by Melinda May who she turns off because this May is now an LMD, with the real one at Radcliffe's house, though she cuts May's face to keep the appearance of the real May. Coulson finds May who wakes up from an unconscious state, not knowing what happened and not knowing she is an LMD. Aida tries to escape with the Darkhold but is stopped by Alphonso Mackenzie who takes the Shotgun-Axe and decapitates her. Leo Fitz works to reactivate Aida for unknown reasons.
Meanwhile, Vijay Nadeer wakes up to see his sister, Ellen Nadeer. They bond now that he is out of his cocoon, but she secretly plotted something with the Watchdogs to eliminate her brother. She reminds him of how they vowed to stop any aliens after their parents died to the Chitauri in the Battle of New York. She then has the Watchdogs shoot him, but Vijay shows his new power, enhanced reflexes. Jemma Simmons shows up to save him, but he still decides to go with his sister, despite her attempts to kill him. On the helicopter, Ellen shoots Vijay and drops him into the ocean.
Holden Radcliffe drinks a beer, remembering Aida, saying that she played her part to perfection. A new Aida agrees with him.
In a press conference officially announcing Quake's involvement with S.H.I.E.L.D., Jeffrey Mace is apart of a failed assassination. Phil Coulson, Mackenzie, and Burrows take Mace away in a Quinjet. The Quinjet is then attacked, leaving Burrows flying out of the Quinjet as it goes down. Now grounded, Mace insists on going to look for Burrows, Coulson believes there is another reason. Meanwhile, real Melinda May wakes up but is quickly subdued by Aida. Mace, Coulson, and Mack find a group of Watchdogs. Mace sees his briefcase and goes to get it. He opens it up to see some blue serum that he tries to inject himself with. Coulson and Mack find him and figure out that he is not Inhuman, but is just using serum to make himself stronger. Mace explains that it is better for publicity and Inhumans themselves if there was an Inhuman Director. Coulson agrees and tells Mace that he will be the Public Director, but Coulson now calls the shots.
Melinda May wakes up and breaks free. She kicks Aida out the window, but it is revealed she is in a simulation. Aida tells Radcliffe that she thought she could keep May calm by making the area peaceful, but she strives on battle. So she used the Darkhold's knowledge to make a better simulation and put her in a realistic replaying of the Rescue in Bahrain, but this time, she saves Katya Belyakov. The reason why Fitz reactivated Aida is because he thinks Radcliffe is planning something. He finds out Radcliffe wants the Darkhold. Holden Radcliffe is arrested and taken into custody, unbeknownst to them that it is an LMD version of him.
Billy Koenig is kidnapped by the Watchdogs because Coulson gave him the Darkhold. Radcliffe, who is now working with the Watchdogs and their leader, Anton Ivanov, uses a device to search Billy's mind. It shows that Billy gave it to his twin, Sam Koenig. It is revealed that the Koenig's passed it around their family and it is hidden away in a maze. May's LMD and Coulson find the Darkhold and May takes it revealing to Coulson that she is an LMD. Radcliffe takes it and leaves the LMD for dead now that her mission is complete. Fitz realizes Radcliffe is an LMD and shoots him, revealing that the LMDs have a Quantum Brain created by Aida when she read the Darkhold. S.H.I.E.L.D. burns Radcliffe's LMD along with Aida's head, but keep May's LMD because if they can't find her, that's all they have.
Anton Ivanov thinks that since Vijay Nadeer is an inhuman, that means that Ellen could be one. He sends Tucker Shockley to expose her to a Terrigen Crystal. When he does, he starts turning into an Inhuman instead and he blows up, killing Senator Nadeer. He reassembles himself and finds out he could explode anytime he wants. When stopping him, Mace decides to be the shield. He stops the Watchdogs but gets taken into custody. However, the team is able to stop Shockley. Meanwhile, Coulson and Mack find out that Aida is based off of a real person named Agnes Kitsworth whom Radcliffe had a personal relationship with before she got sick. They meet her and convince her to help them find Radcliffe. However, when seeing Radcliffe, she decides to join him. At Radcliffe's place, he puts her into the Framework, saying her life will be perfect without the fear of death. She goes under and leaves her body to die, while her mind lives.
Ivanov tortures Mace, saying that he wants Coulson because the agent had indirectly killed all of his friends, years ago. S.H.I.E.L.D. moves in on Mace and saves him, but they get split up. Quake encounters Ivanov and beats him. The team leaves, but Aida comes in and retrieves Ivanov's body. At the base, Fitz-Simmons push and cart into a room and see that the team has returned. An alarm goes off saying the LMD alert has activated and three out of the four agents that have returned are LMDs.
Jemma Simmons looks at the alert for the room that they are in and sees one of them is an LMD as well. She pulls a gun on Fitz who protests that maybe it's her and she doesn't know just like May. They argue while tensions rise, Simmons tells him to slit his wrist so that she could see if he has a sub structure. He complies but a lot of blood comes out. He says he slit his radial artery but tells Simmons not to go near him. She goes to help and he changes his composure and stabs her with a knife, revealing he is an LMD. Simmons wakes up to find the Fitz LMD hooking her mind up to the Framework. She beraks out of her restraints and sends equipment falling on her. She then stabs him multiple times until he dies.
Meanwhile, Johnson does some work and walks into a room to find many Daisy Johnson LMD's. Mack's LMD walks in and she quakes him. Simmons finds Johnson hiding and they prepare to fight but realize that they are both human. They try to escape, Johnson fights Mace's LMD, Coulson's LMD, and Mack's LMD while Simmons gets Piper, James Davis, and Prince to help them escape. Mack sets off off a superpowered quake blast taht's destroys Mack's LMD. They make their way to the exit where they encounter May's LMD, who is sitting on explosives ready to ignite. Coulson walks in to find that she had let them go. May tells Coulson that she was programmed to do things, one thing she wasn't programmed to do was to keep Coulson safe, but he's not Coulson. She then ignites the bomb, killing all of the LMDs including herself, while the team escapes. Meanwhile, Aida asks Radcliffe a moral question, he tells her that they are helping the people because the Framework takes away their one regret, making a better life. She decides the best course of action is to kill him and let his mind live in the Framework.
Johnson and Simmons pick up Yo-Yo Rodriguez and figure out they have to plug themselves into the Framework to get the rest out. They do it. Johnson awakes in a tub to find she has a boyfriend that she thinks is Lincoln Campbell, but it is actually Grant Ward. Coulson is now teaching about how Inhumans are bad, Mack picks up a pink bike off his lawn, Fitz steps out of a fancy car and takes a woman's hand. May stands at the Triskelion, which now has a HYDRA symbol on it. In a graveyard, the wind blows leaves off of a grave, revealing the name "Jemma Anne Simmons." Meanwhile, Ivanov wakes up to find he is now an LMD.
In the Framework, Daisy Johnson goes to wake up her boyfriend, Lincoln Campbell, finally seeing him after his death many months ago. She wakes him up only to find Grant Ward, she tries quaking him but realizes she hasn't gone through Terrigenesis yet. Calling her Skye, he tells her to get ready for work. She opens up her agent badge to see she is an Agent of HYDRA. They are tasked by Melinda May to interrogate possible Inhuman, Jason Rajan, Johnson immediately recognizes him as Vijay Nadeer. However, before getting him to spill, Ward knocks him out witha single punch. From a memorial, Johnson realizes that May didn't kill Katya Belyakov in this reality. This rescue led to many people dying from Belyakov in Cambridge, making everyone fear Inhumans and leading to HYDRA's control. Meanwhile, Jemma Simmons breaks her way out of her own grave, realizing she was shot, and makes her way to the Triskelion.
Phil Coulson, who is now a teacher, lets HYDRA take a suspected inhuman out of his class. He then looks at his many memorabilia like a picture of Lola, that he doesn't fully remember. Simmons visits him, after threatening to call HYDRA, he eventually tries to help her. Johnson is taken to a head of HYDRA, Leo Fitz, The Doctor. Fitz gives her a briefing, then goes to see his lover, the other head of HYDRA, Aida or now known as Ophelia. Alphonso Mackenzie now lives with his daughter, Hope, who had passed away in the real world.
Meanwhile, Simmons and Johnson meet up, but are attacked by HYDRA. Ward comes in and shoots at the agents, revealing he is a part of the Resistance. They go to the Resistance's Base and meet the Patriot, an Inhuman superhero. Simmons tries to tell them the world is fake, but they don't believe it. Coulson, Ward, and Simmons go to Holden Radcliffe's Framework house where he now lives with Agnes Kitsworth. When they get there, they find The Doctor, who was convinced by Aida that Kitsworth is a threat. Ward has a shot on Fitz, but Simmons pleads not to saying he won't harm anyone. Fitz then shoots Kitsworth, killing her.
At the Triskelion, May catches on the Johnson and has Alphonso Mackenzie come in to speak to Johnson. Mack talks to Johnson and tells her he remembers the real world, to Johnson's amazement. When she cracks, he reveals that he had a microphone and May threatened his daughter. Johnson is brought away and tortured. Mack feels so guilty that he joins the Resistance and helps out. Fitz meets up with his father, who is his one regret in the real world, who tells him that Ophelia is getting in his head and causing him to make bad decisions. The Resistance goes to save suspected Inhumans from a concentration camp, and find fellow member, Antoine Triplett, Coulson vaguely recognizes him. May attacks The Patriot after injecting herself with an enhanced strength serum. After beating her, Mace goes into another building, Fitz decides to strike the building leaving it crumpling. Inside, Mace saves a kid by holding up a falling pillar, and yells at everyone to leave. May gives him a nod of respect before leaving. The building then comes crumpling down on Mace, killing him and his real life counterpart.
May decides to leave HYDRA and join the resistance. She breaks Johnson out and gives her her inhuman powers. On their way out, they are stopped by Aida, Johnson quakes her out the window, leaving her fatally injured. Fitz vows to get revenge on them. The Resistance breaks into a TV studio and announce to the world to rise up, with Coulson making the announcement saying he is an Agent of S.H.I.E.L.D.. Meanwhile, Simmons goes to Fitz' house and is found by his father, who attacks her. She accidentally kills his father with Fitz listening on the phone.
Everyone goes to the exit of the Framework. Coulson is shot by HYDRA forces and helped to the edge by May. She worries that this whole thing is fake and their might not be a "real world," Coulson tells her it's a leap of faith and falls into the portal with May following. They awake in the real world, Coulson decides to kill Aida's body unknowing that she has been making herself a biological body. Simmons arrives but is followed by Fitz, who shoots her. He tells her she is nothing to him and makes her say it. Radcliffe comes from behind and hits Fitz saying to remember it's not his own fault and throws him in. Mack sees that the framework gets pixelated when soeone jumps in and realizes the world is fake along with his daughter. It's his turn next, but he asks if Hope is alive in the real world, after learning she isn't he stays. Johnson and Simmons jump in and leave.
In the real world, Aida has made herself her own body and sees Fitz who is confusing his memories between the two worlds. May yells at Fitz to move so she can take a shot, but Aida teleports him away revealing she has all of the inhuman's powers. The team works to save Mack's uncoscious body while the base floods from the ocean around them. Fitz convinces Aida to help and she does, saving Mack. She teleports them to the Zephyr and has a moment of gratitude before Simmons ices her and Fitz. Aida wakes up and goes crazy, attacking everyone and escapes the Zephyr. The team wonders where Yo-Yo Rodriguez is and finds out she has gone into the Framework to get Mack. She wakes up to find Radcliffe saving her and saying the Framework is shutting down and things are disappearing. Meanwhile, Ghost Rider returns from the Dark Dimension and steals his car from a lot.
Aida finds Ghost Rider and attacks him but realizes her powers do nothing. Robbie Reyes reunites with S.H.I.E.L.D. and they think of plans. Meanwhile at a government meeting, Glenn Talbot gives a speech but is shot by a Daisy Johnson LMD made by Aida. The team comes in too late and Talbot is carted away. Reyes and Coulson have a plan and lead Aida to Fitz. Aida kills Simmons while Fitz watches, but it is actually a Jemma Simmons LMD, Aida is then suprised by real Simmons who shoots her. Coulson goes to Aida and turns into Ghost Rider. He then burns her alive.
Meanwhile, Rodriguez finds Mackenzie and tries to tell him that they love each other but sees Hope. She accidentally tells Hope that she isn't real which angers Mack. Everything around them is disappearing which scares Hope. Mack hugs her saying he will never let her go, she then disappears from his arms while he cries. Rodriguez and Mackenzie then leave the Framework. Coulson and Reyes talk and Coulson tells Reyes not to talk about the deal they made with the Spirit of Vengeance. Reyes then takes the Darkhold and leaves Earth, going into the Dark Dimension. Radcliffe, being the only person left in the Framework, pours himself some scotch and watches the sunset until he disappears from existence. The team gets something to eat at a diner before they eventually get arrested for the attempted murder of Glenn Talbot. The power then goes out and the team is frozen in place by a mysterious man. Coulson awakes in am unknownplace and opens the barriers to the window looking out onto Space. He says it's time to get to work.
- Clark Gregg as Phil Coulson / Phil Coulson LMD
- Ming-Na Wen as Melinda May / Melinda May LMD
- Chloe Bennet as Daisy Johnson/Quake/Skye / Daisy Johnson LMD
- Iain De Caestecker as Leo Fitz/The Doctor / Leo Fitz LMD
- Elizabeth Henstridge as Jemma Simmons / Jemma Simmons LMD
- Henry Simmons as Alphonso Mackenzie / Alphonso Mackenzie LMD
- John Hannah as Holden Radcliffe / Holden Radcliffe LMD
- Gabriel Luna as Robbie Reyes/Ghost Rider
- Natalia Cordova-Buckley as Agent Yo-Yo Rodriguez
- Mallory Jansen as Aida / Agnes Kitsworth
- Lorenzo James Henrie as Gabe Reyes
- Lilli Birdsell as Lucy Bauer
- Briana Venskus as Agent Piper
- Max Osinski as Agent James Davis
- Ricardo Walker as Agent Prince
- Blaise Miller as Agent Nathan B. Nathanson
- Jason O'Mara as Jeffrey Mace/Patriot / Jeffrey Mace LMD
- Ward Roberts as Hugo
- Usman Ally as Vincent
- Patrick Cavanaugh as Agent Burrows / Agent Burrows
- Parminder Nagra as Senator Ellen Nadeer
- José Zúñiga as Eli Morrow
- Kerr Smith as Joseph Bauer
- Manish Dayal as Vijay Nadeer / Vijay Nadeer
- John Pyper-Ferguson as Tucker Shockley
- Adrian Pasdar as Brigader General Glenn Talbot
- Zach McGowan as Anton Ivanov/Superior
- Brett Dalton as Grant Ward
- Jordan Rivera as Hope Mackenzie
- B.J. Britt as Antoine Triplett
- David O'Hara as Alistair Fitz
|The Ghost||4.01||September 20, 2016||Jed Whedon & Maurissa Tancharoen||Billy Gierhart|
|Ghost Rider is coming, and S.H.I.E.L.D. will never be the same.|
|Meet the New Boss||4.02||September 27, 2016||Drew Z. Greenberg||Vincent Misiano|
|Daisy goes to battle Ghost Rider at a terrible cost, and Coulson faces the new Director, and his bold agenda surprises them all.|
|Uprising||4.03||October 11, 2016||Craig Titley||Magnus Martens|
|As Coulson, Mack and Fitz attempt to track down and neutralize a rogue group looking to end Inhuman Registration worldwide, Simmons and Dr. Radcliffe only have hours to save May before she succumbs forever to her mysterious illness.|
|Let Me Stand Next to Your Fire||4.04||October 18, 2016||Matt Owens||Brad Turner|
|As Ghost Rider's quest for vengeance brings him into an explosive confrontation with S.H.I.E.L.D., Coulson and Mack must rely on an unlikely ally in their time of desperate need; and Daisy reunites with a familiar face to stop the Watchdogs.|
|Lockup||4.05||October 25, 2016||Nora Zuckerman & Lilla Zuckerman||Kate Woods|
|As Robbie Reyes struggles to control the Ghost Rider; S.H.I.E.L.D. infiltrates a high-security prison to unravel the secrets that haunt them all.|
|The Good Samaritan||4.06||November 1, 2016||Jeffrey Bell||Billy Gierhart|
|Robbie's shocking story on how he became Ghost Rider is finally discovered as Coulson and his team's lives hang in the balance.|
|Deals With Our Devils||4.07||November 29, 2016||DJ Doyle||Jesse Bochco|
|With the loss of half the team, the remaining members search for answers as the clock counts down for Ghost Rider.|
|The Laws of Inferno Dynamics||4.08||December 6, 2016||Paul Zbyszewski||Kevin Tancharoen|
|S.H.I.E.L.D. and Ghost Rider find themselves unlikely allies when the lives of all of Los Angeles hang in the balance.|
|Broken Promises||4.09||January 10, 2017||Brent Fletcher||Garry A. Brown|
|Coulson is unaware of a dark secret May is hiding, even as the two grow closer; Aida is determined to find the Darkhold.|
|The Patriot||4.10||January 17, 2017||Sharla Oliver & James C. Oliver||Kevin Tancharoen|
|Separated from their team, Coulson and Mack discover a shocking secret about Mace, leaving all of S.H.I.E.L.D. in a precarious position.|
|Wake Up||4.11||January 24, 2017||Drew Z. Greenberg||Jesse Bochco|
|May works to uncover the truth about what happened to her; Aida's next move puts everyone's life at risk.|
|Hot Potato Soup||4.12||January 31, 2017||Craig Titley||Nina Lopez-Corrado|
|Agents Sam and Billy Koenig are hunted down to get at the Darkhold book, and only Phil Coulson and the team can save them before the clock ticks out.|
|BOOM||4.13||February 7, 2017||Nora Zuckerman & Lilla Zuckerman||Billy Gierhart|
|Daisy, Director Mace and the S.H.I.E.L.D. team must find a way to contain an explosive Inhuman. Meanwhile, Coulson and Mack come face-to-face with Radcliffe’s inspiration for Aida.|
|The Man Behind the Shield||4.14||February 14, 2017||Matt Owens||Wendey Stanzler|
|Mace fights for his life while Coulson and team find themselves in a deadly cat-and-mouse game as they attempt his rescue.|
|Self Control||4.15||February 21, 2017||Jed Whedon||Jed Whedon|
|Suspicion turns to paranoia when the team doesn't know who can be trusted as more LMDs infiltrate S.H.I.E.L.D.|
|Agents of HYDRA|
|What If...||4.16||April 4, 2017||DJ Doyle||Oz Scott|
|Daisy and Simmons uncover secrets and lies in a world gone mad. With HYDRA in control, they are our only hope to save everyone.|
|Identity and Change||4.17||April 11, 2017||George Kitson||Garry A. Brown|
|As Daisy and Simmons struggle to discover an escape route to the real world, the identity of the Inhuman leader of the Resistance is revealed.|
|No Regrets||4.18||April 18, 2017||Paul Zbyszewski||Eric Laneuville|
|The truth behind Fitz's turn could bring down all of S.H.I.E.L.D..|
|All the Madame's Men||4.19||April 25, 2017||James C. Oliver and Sharla Oliver||Billy Gierhart|
|Daisy finds herself teamed up with an unlikely partner. Meanwhile, Aida prepares to put her ultimate end game into effect.|
|Farewell, Cruel World!||4.20||May 2, 2017||Brent Fletcher||Vincent Misiano|
|The clock is ticking for Daisy and Simmons to get the team out of the Framework, but not everyone is ready and willing to leave.|
|The Return||4.21||May 9, 2017||Maurissa Tancharoen and Jed Whedon||Kevin Tancharoen|
|Coulson and the team's victory in the Framework is short-lived, as an even deadlier enemy looms against them all.|
|World's End||4.22||May 16, 2017||Jeffrey Bell||Billy Gierhart|
|With the surprising emergence of Ghost Rider, Coulson and the team attempt to stop Aida from ending the world.|
- This is the first season of Agents of S.H.I.E.L.D. where the Kree don't appear.
- This is the first season where a series regular is credited as recurring or guest.