After escaping Fox River, Michael Scofield and his fellow convicts scatter across the country, each pursued by law enforcement. The group includes Lincoln Burrows, Michael’s brother; Fernando Sucre, who wants to reunite with his fiancée; and T-Bag, a dangerous fugitive. Meanwhile, Agent Alexander Mahone, a determined FBI profiler, is assigned to track them down. The escapees must evade capture while dealing with their own personal struggles and conflicting goals.
Michael’s plan relies on a series of clues hidden in his tattoos, leading to buried money in Utah. However, tensions rise as trust among the fugitives begins to fray. T-Bag betrays the group, taking a key clue for himself, while others like C-Note and Tweener go their separate ways. Meanwhile, Lincoln seeks to clear his name by uncovering the conspiracy behind his framed murder charge. The hunt intensifies as Mahone proves to be a relentless adversary.
As the fugitives navigate dangerous situations, their pasts catch up with them. Sucre risks everything to reach his fiancée, while Sara Tancredi, the prison doctor who helped Michael, faces legal consequences. The mysterious Company, responsible for framing Lincoln, continues to manipulate events from the shadows. Michael and Lincoln uncover more about the conspiracy, but their efforts are constantly thwarted. The pressure mounts as the fugitives realize they can’t outrun their pursuers forever.
Betrayals and alliances shift as the season progresses. T-Bag’s violent nature resurfaces, while others like Haywire and Tweener meet tragic ends. Michael and Lincoln eventually recover the stolen money, but Mahone closes in on them. Meanwhile, Sara goes on the run after being framed for murder, joining forces with the brothers. The Company’s reach extends further, implicating high-ranking officials. The stakes grow higher as the fugitives prepare for a final confrontation.
The season climaxes with Michael, Lincoln, and Sara attempting to flee to Panama, but their plans are disrupted when Mahone corners them. In a desperate move, Michael surrenders to save his brother, while Sara escapes. The season ends with Michael being imprisoned in Sona, a brutal Panamanian prison, setting the stage for the next chapter. The fugitives’ fates remain uncertain as new dangers and alliances emerge in their ongoing fight for freedom.