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.
Michael seeks help of his fellow prison inhabitants to execute his escape plans.
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 nicknamed Haywire, who never sleeps.
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.
Kellerman and Hale blackmail Warden Pope. Michael finds out he might get out earlier than anticipated. Veronica becomes uncertain of her allies.
Michael creates a lock-down 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.
While the riot intensifies, Abruzzi and Sucre join forces. Michael must decide whether or not to save the life of Dr. Tancredi.
Michael finds out a storeroom fundamental to his escape plans has been converted into a break room. Veronica and Nick are being threatened.
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 escape gang and Dr. Sara are shocked when they learn the identity of Michael's latest visitor, who brings with her a priceless piece of the plan; Bellick's suspicions are aroused; Tweener's pickpocketing skills get Michael back some valuable time. Quinn tracks Veronica, Nick and LJ to the cabin in the woods and Kellerman and Hale have a life-threatening difference of opinion.
With proof that his escape plan is working, Michael gets suited up to overcome the vertical limits of his last obstacle. Back in PI, as the escape attempt draws near, the group tries to reduce their number by one and targets T-Bag, who has some insurance in his pocket. Outside the prison walls, LJ slips away to attend his mother's funeral, which is also attended by her murderer. Veronica gets a call from an unlikely source who sheds light on the night of Terrence Steadman's assassination.
With Lincoln's execution scheduled for the following day, Veronica comes out of hiding to reach out to him and gains a newsworthy ally in the process. Kellerman makes the ultimate sacrifice to preserve the conspiracy. Michael must find a way to get Lincoln out of Solitary confinement in time for the escape that evening. The inmates risk everything as they attempt the escape.
A CO and his supervisor notice that the utility room's frosted glass door has been broken. They do some investigation and find two pieces of broken pipe. Nick and Veronica ask a judge to grant a stay of execution for Lincoln. In the meeting, there is also a man named Peter Tucci who presides over Respondent's table (aka makes it his mandate to destroy Nick and Veronica's case). Sucre and T-Bag face off during rec time. Sucre is sick and gets a guard's sympathy. Lincoln demands to see Michael but Stolte denies it.
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.
Transferred to the psych ward, Michael tries to clear Haywire's head and jog his memory of the missing piece of the blueprint tattoo; Bellick wants to auction off Michael's cell to the highest bidder; C-Note and T-Bag must team up in a high-stakes poker game, while Sucre's cousin Manche seems to hold all the cards.
The mystery man reveals himself to Lincoln as well as his connection to some bad company; when Michael realizes Sara holds the key to the escape plan, he takes their relationship to another level; Fox River turns into a mob scene when a familiar face returns; Tweener must choose sides; and Bellick may finally discover the "hole" truth.
Westmoreland uses Bellick to plug a hole in the escape plan, which forces Michael to move up the breakout timetable. A fearful Tweener pledges his loyalty to Michael and in return may get out of jail for free; Michael feels that he has no choice but to involve Sara in the plan and must betray his father figure; and Veronica finds her life in jeopardy from her closest ally, who has a surprising connection to a Fox River inmate.
Dr. Sara 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. Michael, Lincoln and the other inmates make a break for it, but after the alarm is sounded, find out who will make it over the wall, who will be left behind and who will leave the prison in a body bag.
With the escape in motion, Michael, Lincoln and the inmates take flight outside the prison walls, risking life and limb to evade capture. Warden Pope and Captain Bellick embark on a relentless pursuit to capture the escapees; the Vice President fears she will lose her command as well as her life; and Veronica tracks down the most significant piece of evidence to prove Lincoln's innocence.