Due to a political conspiracy, an innocent man is sent to death row and his only hope is his brother, who makes it his mission to deliberately get himself sent to the same prison in order to break the both of them out, from the inside out.
Michael Scofield, a structural engineer, attempts to rob a bank in order to get incarcerated at Fox River State Penitentiary, where his brother Lincoln Burrows, accused of murdering the Vice President's brother, is scheduled to be executed. At Fox River, Michael approaches a number of inmates, all of whom play an important role in his plan to free his brother from the inside. Meanwhile, agents Kellerman and Hale are determined to make sure the execution goes through as planned. Lincoln's son LJ gets into trouble.
When Michael reveals his escape plan to Sucre, Sucre chooses to be no part of it, and requests a cell transfer. Michael gets a new cellmate called Haywire.
Veronica keeps uncovering new information regarding Lincoln's case and decides she wants to work on the case full-time. When no one wants to help her on the case, Nick Savrinn (an attorney) offers his assistance and the two of them visit Lincoln.
Michael creates a lockdown by sabotaging the air conditioning in order to execute his breakout plan properly, and unintentionally causes a riot that gets Sara into huge trouble. Meanwhile, an ex-con is blackmailed into seeing to that Lincoln is killed.
Abruzzi's demotion in the prison hierachy puts the entire escape plan at risk. Michael finds himself in the uneviable position of trying to protect T-Bag's new "fish" and facing the threat of T-Bag exposing the plan to the guards. The inmates dig themselves into a hole.
Michael is forced to give up Fibonacci's location to Philly Falzone, and Kellerman and Hale get a little unwanted help to track down LJ who has gone missing. Veronica and Nick uncover evidence against the man Lincoln was convicted of murdering.
The escapees and Dr. Tancredi are shocked when they learn the identity of Michael's visitor, who brings with her a very important piece of the escape plan.
Michael sees proof his plan is working, so he begins to overcome the last obstacle. As the escape draws near, the group tries to reduce its number by one and targets T-Bag.
With Lincoln's execution scheduled for the following day, Veronica comes out of hiding to contact him and gains an ally. Kellerman makes the ultimate sacrifice to preserve the conspiracy. Michael looks for a way to get Lincoln out of solitary confinement in time for the escape that evening. The inmates risk everything as they attempt their escape.
As Lincoln is about to be executed, he briefly sees his father in the viewing room. A phone call from judge Kessler delays the execution. After reviewing the newly surfaced evidence, the judge orders the exhumation of Steadman's body.
Michael creates a new, more dangerous, break-out plan, involving going through the prison yard. An accident puts Michael's new plan in danger.
Flashbacks shed light on the past actions that led to the incarceration of Lincoln, Sucre, T-Bag and C-Note. Basis of Michael's ingenious break-out plan are revealed. Dr. Tancredi memorizes how she ended up in Fox River State Penitentiary.
Lincoln is worried about Michael's sanity while Michael has trouble remembering some parts of the prison schematics. Sucre has to conceal the hole in the guard's break room. Warden Pope transfers Michael to solitary after he declines his request.
In an effort to recreate the missing piece of the tattoo, Michael gets transferred to the psych ward, seeking the help of Haywire. T-Bag and C-Note have to join forces.
Michael must get the key to the infirmary and enlist the help of an old face, while Lincoln learns the identity of his kidnapper and another inmate learns of the escape.
Westmoreland wants Michael to speed up the planned escape, and gets Bellick one step closer to unraveling it. Michael has to decide whether to involve Sara in the breakout plan. Tweener's devotion is put to a test. Veronica finds out that her ally unexpectedly has a connection to an inmate serving time at Fox River.
Everyone's ready to make their escapes across the high wire. Veronica and Nick realize they may be in over their heads. And Agent Kellerman helps Vice President Reynolds calm down before her debate.
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.
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