Daniel Sousa became a high-ranking S.H.I.E.L.D. agent because of various heroic acts such as defeating the Council of Nine. However, by 1955, Sousa became suspicious that S.H.I.E.L.D. had been infiltrated by HYDRA. He submitted a report to the CIA, although it was ignored. Sousa then informed his superior officer, Wilfred Malick, regarding his suspicions, unaware that Malick was a high ranking HYDRA member himself.
Sousa was asked to bring Howard Stark an item that would help him, and Sousa agreed. His contact, Niles Lindmore, met Sousa at Area 51, where he gave Sousa the item in a briefcase. Sousa took the train to Hotel Roosevelt, where he planned to deliver the item.
Daniel Sousa waited in the lobby of Hotel Roosevelt to give a signal, and then followed the concierge into the hotel. Meanwhile, a HYDRA agent followed Sousa in the hotel. Sousa successfully made the delivery, but the agent found and shot Sousa, killing him. The police later arrived and took his body.
Daniel Sousa's death became notable in S.H.I.E.L.D., who believed him to have been killed by Russian agents. His story was taught to every student at S.H.I.E.L.D. Academy, and he became known as the first fallen S.H.I.E.L.D. Agent. Phil Coulson learned about the story and admired Sousa's bravery, considering him a hero.
In 2019, Chronicom Hunters began traveling back in time in order to prevent S.H.I.E.L.D. from existing and claim Earth for themselves, creating an alternate timeline in the process. They traveled to July 1955 and replaced Niles Lindmore with one of their own in order to infiltrate Area 51. After S.H.I.E.L.D. followed the Chronicoms through time, Jemma Simmons and a Life-Model Decoy of Phil Coulson ran into Daniel Sousa.
The following day, Coulson realized that the date was July 22, 1955 and Sousa was meant to die that day, although not before noting that history had already been veered off track. In order to preserve the timeline, Coulson aided Sousa in making the delivery the same way he was meant to, despite new interference sent by Wilfred Malick, with tips from Luke. Sousa successfully made the delivery the same way he had in the original timeline, but Alphonso Mackenzie, unaware that they were in an alternate timeline, elected to alter what he believed was the prime timeline and save Sousa from being murdered. Knowing Sousa's route, Coulson interfered and shot Sousa with an I.C.E.R.. He then took Sousa's place, getting shot instead. His LMD physiology allowed him to survive as he fell into the pool and was later retrieved by Jemma Simmons and Daisy Johnson.
Sousa was then brought aboard Zephyr One, where Coulson informed him that he was meant to die according to history and that he could not reside in 1955 anymore since they had faked his death. Sousa realized that his saviors were agents of S.H.I.E.L.D. from the future, and accepting his new path, joined their team. He aided them in their mission to stop the Chronicoms, and time-traveled with them to 1973, 1976, 1982, and 1983. He then traveled to 2019 of his new friends' timeline and resided there permanently, becoming Daisy Johnson's boyfriend.