Michael Scofield commits a bank robbery so that he can be put into a prison with his brother, Lincoln Burrows, who was sentenced to death for a murder he swears he didn't commit -- the murder of the Vice President's brother.
Michael continues to plan his and his brother's escape. His path crosses an inmate named T-Bag when he tries to remove a screw from some bleachers. Mafia friends of Abruzzi visit and put pressure on him to get an informant's whereabouts from Michael.
After cutting off Michael's toe, Abruzzi tries to befriend him in an effort to learn the whereabouts of the snitch. Sucre not only turns Michael down for help in the prison break, he gets a cell transfer and Michael's new cellmate, straight from the psycho ward, is even less helpful.
Michael's odd cellmate Haywire fixates on his tattoo. Sucre reconsiders Michael's offer of escape when he learns of Maricruz's indiscretions. Lincoln has awful nightmares about his eventual execution.
Kellerman and Hale demand Michael's transfer from the prison which makes him push up his timetable and cut down his escape party to one. Michael reveals to the warden, and therefore the entire prison, that Lincoln is his brother.
A riot breaks out in the prison, endangering lives and the plan. Nick and Veronica follow clues to Washington, D.C. after Nick reveals that the call that busted Lincoln the night of the murder came from there. Lincoln tries to protect a C.O. Sara is endangered by the inmates in the infirmary as the riot spreads.
Michael attempts to save the life of Dr. Sara even as Abruzzi and Sucre work at breaking through a wall. An inmate attacks Lincoln in an attempt to kill him. Veronica and Nick have their lives threatened as they follow leads to prove that Lincoln was set up.
Michael must enlist the help of Westmoreland when he discovers that a shack critical to the escape plan has been changed into a C.O. space. LJ's mother and stepfather are killed by the Agents and while he evades their capture, he's set up for the murders.
When Abruzzi can't make payments to Bellick, the crew is shifted from their P.I. duty and it endangers the escape plan. T-Bag tries to pick up a new arrival when his previous one kills himself. LJ is trailed by the Secret Service Agents, but finds his way to Nick and Veronica. Sara learns more about Michael as a person when she visits a former psychiatrist who treated him.
Philly demands Fibonnaci's location in exchange for returning Abruzzi to power and Michael has to contemplate the worth of the plan versus the life of an innocent man. The Vice President calls in assistance and the man immediately seizes control from Kellerman and Hale and tracks down Veronica's hidden location. Yet another inmate learns of Michael's plan to escape and joins his team.
Quinn discovers the cabin in the woods with LJ, Nick and Veronica in it. Michael's wife comes to the prison for a conjugal visit and delivers him a credit card.
The group learns that all seven of the escapees won't be able to make it. T-Bag comes forward to squash any ideas of cutting him out by saying that he's told someone on the outside about the escape plan as insurance.
Abruzzi is airlifted out after his run-in with T-Bag. Michael is denied access to Lincoln by the warden after Lincoln is separated from the population because of the attack on a guard. Michael leads the team towards freedom with the execution looming, but they hit a snag when a grate has been replaced and Michael can't compensate.
Michael and the rest of the prisoners stealthily sneak back into their cells, and Michael decides to try and defuse the electric chair's circuitry. Nick and Veronica try to get a stay of execution for Lincoln, while Sara tries to get her governor father to examine Lincoln's situation.
Veronica revisits the deceased Steadman’s body as Lincoln awaits his execution and begins to have terrible visions of his past. Meanwhile, Michael tries to devise a new plan while tackling responsibilities as a guard.
The story behind Lincoln’s imprisonment becomes known, along with that of C-Note, T-Bag and Sucre, while Dr Tancredi goes into detail about her arrival at the penitentiary. Meanwhile, more of Michael’s plan comes to light.
When Michael won't name names, Warden Pope places him in solitary. Lincoln fears for Michaels sanity, Sara is determined to figure out his secrets and Michael is struggling with some missing pieces of the prison schematics.
Michael attempts to remind Haywire about the missing piece of the blueprint tattoo, while Bellick would rather auction Michael's cell off to the highest bidder. C-Note and Tea-Bag hook up in a high stakes, winner take all poker game but Sucre's cousin seems to be in control of this match.
Michael is ready to take his relationship with Sara to the next level, but it's not because of love. A well connected man reveals himself to Lincoln, Tweener has a decision to make as to what side he's on and Bellick may finally learn the whole truth.
Bellick attempts to plug a hole in the escape plan under instruction from Westmoreland forcing Michael to have to shorten the timetable. Michael feels he now has no choice but to include Sara in the plan, betraying his father figure.
Dr. Sarah questions if she should leave a light on and the door open for Michael, who must betray the Pope in order to carry out his escape plan. Veronica finds evidence that points her to Montana, but realizes that her closest ally may actually be her greatest enemy.
As the escape is in progress, Warden Pope and Captain Bellick begin a search to detain the escapees. Michael and co. have to reach the aircraft fast as the police is hot on their heels. Veronica discovers a major piece of evidence that could prove Lincoln's innocence. The Vice President is worried about losing her authority.