- "You may be noticing that the Lighthouse is going into lockdown mode. This is not a drill. The Lighthouse is keeping us safe. All exits, including the hangar, have been sealed to protect us from any outside intrusion. Which is good, 'cause there is currently a sizeable alien spaceship overhead. Oh, and due to a technical malfunction, the Lighthouse thinks we're under nuclear attack, so we may be trapped inside for 15 years... ish."
- ―Phil Coulson[src]
The Siege of the Lighthouse was the result of General Hale revealing the location of the Lighthouse, which she had obtained from the Faustus-indoctrinated Glenn Talbot, to Confederacy leader Qovas, who was also informed that S.H.I.E.L.D. had a cache of Gravitonium. Qovas sent a number of Remorath warriors into the base to obtain the Gravitonium, killing several S.H.I.E.L.D. agents in the process. As the Remorath almost overwhelmed the agents in the Lighthouse's control room, Talbot infused himself with the cache of Gravitonium the Remorath were searching for, and, with the new powers he obtained as a result, crushed nearly all Remorath warriors in the Lighthouse, ending the siege.
Upon finding a transceiver, the secret organization HYDRA made contact with the Confederacy, an alliance of extraterrestrial races. The Confederacy warned HYDRA, and especially its leader General Hale, of an impending conflict which could severely affect Earth. The Confederacy offered its protection in exchange for Inhumans and Gravitonium. Hale accepted the deal, but secretly worked to alter it by infusing someone with the Gravitonium to create a super soldier which would show the Confederacy that Earth could defend itself.
However, Hale's plans did not go as expected. S.H.I.E.L.D. leader Phil Coulson refused to assist Hale for he had seen the consequences of the Project Destroyer of Worlds in the future. Moreover, Hale's daughter Ruby Hale rebelled against her mother and stole the Gravitonium HYDRA had reclaimed in the ship Principia.
Ruby attempted to infuse herself with the Gravitonium, but the process turned out to be incredibly painful and a distressed Ruby ended up murdered by Yo-Yo Rodriguez. Upon losing her daughter, Hale returned to Confederacy member Qovas and informed him that S.H.I.E.L.D. had reclaimed the Gravitonium he was looking for and that she would not try to stop him from attacking S.H.I.E.L.D. Indeed, thanks to a Faustus indoctrinated Glenn Talbot, HYDRA and the Confederacy knew the coordinates of the S.H.I.E.L.D. base, the Lighthouse.
Using his Phase Harmonic Teleportation Device, Qovas transported his spaceship over the Lighthouse, which was immediately noticed by S.H.I.E.L.D.. The emergency protocols of the Lighthouse were activated, but Phil Coulson failed to listen to all available options, triggering the complete lockdown of the base for fifteen years according to the nuclear apocalypse protocol. Right after that, Qovas contacted the Lighthouse and demanded to be handed over the Gravitonium, but Coulson blatantly refused, claiming that the Lighthouse could withstand a several years long siege.
Yo-Yo Rodriguez, who just had an argument with Alphonso Mackenzie, and Melinda May joined Coulson in the control room. May revealed that Daisy Johnson had left the Lighthouse to investigate a potential lead on a way to cure Coulson from his condition. As Rodriguez and May argued over this decision, Coulson realized that the Remorath could easily bypass the Lighthouse's lockdown by using their teleportation device. Indeed, Qovas sent a battalion of Remorath into the base, which was soon discovered by Deke Shaw, who saw Agent Thomas being stabbed in front of him. Shaw hid in an air vent, witnessing the murder of another S.H.I.E.L.D. agent.
Shaw managed to reach the control room and told his friends what he knew about the Remorath. Facing such a threat, Coulson decided to find a way to leave the Lighthouse in spite of the confinement protocols. Leo Fitz left the labs with Agent Wahl to find a way to override the lockdown's control; Yo-Yo Rodriguez was tasked to escort Glenn Talbot to safety, Jemma Simmons, Davis and Piper had to prepare to take the Gravitonium onto the Zephyr One which would be prepared by Mackenzie and Shaw.
On their way, Fitz and Wahl made their best to avoid the Remorath roaming in the Lighthouse, but Wahl ultimately got killed by one of them. Fitz ran away and found Shaw, who briefly incapacitated the Remorath with a fire extinguisher, enabling them to flee and hide to safety. However, they also discovered that the override system Fitz planned on hacking into was destroyed, keeping S.H.I.E.L.D. from escaping the Lighthouse. They reported it to Coulson, who ordered everyone to secure as many weapons as they could and get back to the control room. Therefore, Agent Kim left for the armory to find some weapons.
However, Rodriguez and Talbot were unable to reach the control room as there were too many Remorath in the base and they retreated into the lab with Simmons, Davis and Piper. Knowing that the Remorath would come for the Gravitonium, Rodriguez, Davis and Piper left to defend it, leaving Simmons and Talbot in the lab itself. Meanwhile, Mackenzie went to find Fitz and Shaw and escorted them back to the control room, all the while being chased by several soldiers.
Two main battles took place in the Lighthouse, with Rodriguez, Piper and Davis defending the lab while the rest of the S.H.I.E.L.D. team was surrounded by Remorath soldiers in the control room. Using guns, metal rods and Mackenzie's Shotgun-Axe, Coulson, May, Fitz, Mackenzie, and Shaw did their best to repel the invaders, but the Remorath were far too resistant and the agents soon realized that they would run out of ammunition. Meanwhile, Rodriguez, Davis and Piper could not stop the Remorath from going behind them and breaking into the lab.
However, in the meantime in the lab, Talbot had discovered the Particle Infusion Chamber reclaimed from HYDRA. Seeing it as an opportunity to make amends for his past mistakes, Talbot incapacitated Simmons with an I.C.E.R.. He then reclaimed the key of his handcuffs and broke free before reactivating the infusion process and entering the chamber. Although the infusion was incredibly painful, Talbot endured the whole process and stepped out of the chamber with gravity manipulation powers.
Using these newfound abilities, Talbot crushed the Remorath attacking the lab. He then easily made his way through the Lighthouse, killing the invaders he encountered, and reached the control room, where he further exterminated the Remorath soldiers attacking the S.H.I.E.L.D. agents as Coulson was on the verge of being killed. Still shocked by the reveal, Coulson then saw Talbot using his powers to lift a chunk of concrete with Coulson and Talbot himself on it. Together, Talbot and Coulson left the Lighthouse under the stunned eyes of the other agents.
Using his newfound powers, Glenn Talbot took Phil Coulson and himself onto Qovas' Ship, where they quickly confronted Qovas and his Remorath soldiers. During the meeting, Coulson grew more and more worried as Talbot displayed clear signs of mental instability, violently ordering Qovas and the Remorath to kneel before him. In the end, Talbot would become S.H.I.E.L.D.'s new enemy when he arrived to the conclusion that Coulson kept betraying him.
Alphonso Mackenzie patrolled the Lighthouse to make sure that all the Remorath had been eliminated. As one soldier, Qajax, had survived, he was captured and taken prisoner by S.H.I.E.L.D. despite using the Odium to fight against Mackenzie. S.H.I.E.L.D. interrogated Qajax, but he gave no useful answers. However, this enabled S.H.I.E.L.D. to collect some Odium.
Due to Coulson and Talbot, who they still considered an ally as they had no idea what was happening on the spaceship, having left into an hostile spacecraft, S.H.I.E.L.D. decided to set up a rescue mission for both of them. Mackenzie managed to equip the Zephyr One with new thrusters enabling it to be taken into outer space. Quake, Melinda May, Deke Shaw, and Davis thus left in order to infiltrate the Remorath spaceship.