Michael Scofield is a desperate man in a desperate situation. His brother, Lincoln Burrows, was convicted of a crime he didn't commit and put on Death Row. Michael holds up a bank to get himself incarcerated alongside his brother in Fox River State Penitentiary, then sets in motion a series of elaborate plans to break Lincoln out and prove his innocence. Once out of jail, their perils aren't over - the brothers must flee to escape recapture and battle an intricate political conspiracy that puts everyone's life at risk.
Eight hours after escaping from the penitentiary, the fugitives find themselves hard-pressed to evade their captors - but Michael has a plan to get them to safety.
Lincoln enlists Michael in his plan to free LJ from the courthouse, but Mahone stands ready to spring his trap. Meanwhile, T-Bag forces a veterinarian to give him medical attention.
As Mahone closes the gap, Michael and Lincoln resort to desperate measures to evade the tenacious lawman. Meanwhile, Sara is arrested after being released from hospital.
Bellick and Geary track down Michael, Lincoln and Nika and claim they want to help them find Westmoreland's hidden money, and Mahone refuses to believe the brothers are dead.
Michael and Lincoln cross paths with T-Bag and Tweener when the fugitives arrive in Toolele, while Sucre heads to Las Vegas to prevent his ex-girlfriend's wedding.
The escapees discover Westmoreland's money is now buried beneath a housing estate. Governor Tancredi becomes suspicious of Kellerman, and Mahone closes in on the fugitives.
As the gang closes in on the money, Michael's plan begins to unravel. Meanwhile, Lincoln receives some exciting news.
Sucre's plan to escape with the money backfires and, as the police grow dangerously close, his life is left in Michael's hands. Kellerman sets a trap for Lincoln.
Michael questions Mahone's ex-wife, hoping to convince his pursuer to ease up on the hunt, while the FBI stakes out C-Note's reunion with his family.
Lincoln and LJ are liberated by mysterious rescuers, while Sara and Michael are finally reunited. T-Bag tries to keep the money's whereabouts a secret.
Michael tries to con his way onto a plane to Panama. Lincoln confronts his father Aldo, while Kellerman tortures Sara for information.
Michael nurses his father's wounds when Mahone shoots Aldo during their escape attempt. Sara fights back while Kellerman is distracted, and Bellick is suspected of murder.
Lincoln is joined by Michael to look for Sara and gather the proof he needs to be exonerated. Meanwhile, T-Bag strikes again, Bellick agrees to a deal and Sucre is stranded.
Michael and Lincoln go on the run with Kellerman, who reveals he knows a way to exonerate the fugitives. Bellick makes an error of judgement which could prove fatal.
Terrence Steadman's death seriously hampers the plan to prove Lincoln's innocence. Meanwhile, Sucre reaches Mexico but is pulled over by the police.
Michael, Lincoln, Kellerman and Sara head for Chicago in a bid to uncover the conspiracy, while C-Note attempts to calm down a robber when a hold-up gets out of hand.
Michael and Sara look for a former warden to retrieve information that could bring The Company down. Mahone corners another runaway, and C-Note fears for his daughter's life.
The brothers contemplate a way to get the recording to someone they can trust. Agent Kim places pressure on Mahone, and T-Bag steals the identity of a psychiatrist.
Michael and Lincoln attempt to blackmail the president into giving them a pardon. T-Bag's plan to flee the country is put in jeopardy and Sucre comes face to face with Bellick.
Sara gives herself up so that Michael and Lincoln can escape to Panama. Meanwhile, Bellick and Sucre track down T-Bag in Mexico and C-Note is asked to testify against Mahone.
Michael walks into a trap after returning to Panama City to track down the murderous T-Bag. Sara receives unexpected help as her trial gets underway.
Michael comes up with a risky plan to rescue Lincoln from Mahone. Sara is shocked when Kellerman testifies at her trial, and Sucre tries to reunite with Maricruz.