Michael Scofield is imprisoned in Fox River State Penitentiary. He finds his brother, Lincoln Burrows, who is a death row prisoner, and tells him that he is going to break them both out of the prison.

Trouble is inevitable in the prison, with a race riot imminent. Michael has problems retrieving a screw from the bleachers. Veronica receives a security tape that shows Lincoln shooting Terrence Steadman.

Michael gets more of the tools and people he needs, but someone very high up has taken notice and started wondering what he's up to.

C-Note overhears Michael and Lincoln discussing that there are too many fugitives for available time and they share the information with the group telling that one shall be left behind. T-Bag feels threatened and calls his cousin James Bagwell, disclosing the escape plan and asking James to call the Warden Pope in case T-Bag does not contact him later. Abruzzi asks his outside man to kidnap James, but things go wrong and the mobster kills James and his five year old son Jimmy. Abruzzi feels guilty for the death of the child and feels the need of God's forgiveness, but T-Bag betrays Abruzzi like Judas. Meanwhile Veronica and LJ bring Nick to the hospital and while in surgery, LJ escapes to see the funeral of his mother. Daniel Hale sees the teenager in the cemetery but he does not arrest him; later he tells his wife that they should move West and makes an anonymous call to Veronica scheduling a meeting in the Highland Cafe. Maricruz tells Sucre that she is pregnant but she will marry Hector. Captain Bellick presses David to rat Michael, reporting everything he says. Michael tests the escape plan and informs the group that they are ready to go that night, but Lincoln was sent to solitary confinement protecting his brother.

Flashbacks provide exposition on how the inmates arrived at Fox River Penitentiary from The Company's framing of Lincoln to the creation of Michael's plan to save his brother's life.

Michael Scofield and Sara Tancredi fail to get the tape from the Corona de Oro cigar club in Chicago, where security was at the ready, and turn to former warden Henry Pope, a club member, but he wants to call the police. Michael draws his gun and hands it over to prove his veracity; Sarah convinces him to go in with her late father's humidor key and he finds a computer memory stick. In Mexico, Fernando Sucre has car trouble and gets a ride from an Ixtapa airport security employee who sees his wanted-poster just after they parted at the airport, so he must run with his bride. T-bag and his forced-along family find his own house vandalized and looted except for the family bible, which arouses in him youth memories of his perverted father, and assures Suzy he wants their love and is happy to be infertile, her bloodline should take the Bagwells's place. When she refuses, he locks them up, considers ax-murdering but just leaves them behind. FBI Special Agent Alexander Mahone has tracked down Benjamin Miles 'C-Note' Franklin and his daughter, but lets them escape in a bus rather than shoot the kid. C-Note brings her to a doctor, worried about the kidney disease PKD, but won't allow inserting a catheter, rather turns himself in to Mahone, who is with his own boy in Colorado, and makes a deal to get him Scofield. Pope is out of the club, but is greeted at the entrance by Secret Service Special Agent William 'Bill' Kim whom only Paul Kellerman, watching from a roof with Linc, knows by sight. Michael drives over Kim and gets away with Pope, Sarah and Linc, locking Kellerman out. When Michael tells the others he's prepared to honor his promise to Pope (which the others didn't know about) to turn himself in for his help, Henry hands him the stick and lets them go.

Captain Brad Bellick walks in the FBI office demanding Mahone pay him. Michael and his companions are impressed with the recordings on the stick, but it only helps if Kellerman's contacts in Washington use it right, notably high Justice official Cooper Green, who agrees to meet and cooperate, but is tailed by Kim's men. Linc calls his boy L.J., who refuses to give up his relatively normal life till further notice. Sarah meets Bruce Bennett. Bellick tries to bribe Sucre's incarcerated cousin into betraying his Mexican whereabouts. T-Bag finds therapist Dr. Stammel who looks like him, and murders him to steal his identity. Mahone is ordered to dispose of C-note for good once Kim believes he has Scofield; he promises to keep taking care of C-note's family, but only if he uses the content of a package he'll send to his cell- a noose. Sarah is too late calling Linc the real Cooper Green is in his office, but Michael tricks the fake one who pretended to be asthmatic just in time and knocks him down. Paul Kellerman visits his sister Kristine. Fernando Sucre is in heaven in bed with Maricruz Delgado when their baby kicks. The real Cooper Green could help with the tape, but then finds the memory stick has the copy date, not the recording date without which it is not admissible as proof, only to blackmail the president into signing a pardon.

C-note has jumped with the noose around his neck, but is saved by jailers; he has Mahone told he'll still do it. At a Chicago hotel, president Caroline Reynolds is expected for a speech. Michael sends the real Cooper Green away and agrees a meeting point with Linc and Sarah. Mahone enters Sarah's room and only pretends to fail looking under the bed to trap her, she pretends the brothers left her. In Mexico, T-bag finds Bellick is waiting at the luggage conveyor and must get his from the service side, but the laborer he knocks down falls onto it, so he must run. Lincoln surprises his old mate Derrick Sweeney and calls a favor: three tickets on a freighter for Panama. Kellerman is in position to shoot the fiendish president, but when she's in his sight Michael gets arrested just after shaking her hand, and is interrogated by Kim who demands to be left alone with him, to ask where Linc is, then tries literally to beat it out of him; the president barges in and sends Kim out just when he was about to shoot Michael; he tells her the tape is a delicate conversation she had with her brother after his 'death', and he still has copies at twenty locations. Fernando sees on TV T-bag is in Mexico and was videotaped trying to steal, so he deduces the $5,000,000 must be around and tells Maricruz he'll be right back; at his return only Bellick is there, armed and cuffs Sucre, in order to collect the reward, so Fernando offers to share the $5,000,000 by finding T-bag. Sarah guesses right Mahone is on an addictive drug. Caroline calls Linc, who plays the tape which proves her brother was alive on the isle of Terrence and hated conspiring with her Linc's faked conviction; Michael tells her about his suicide and dares her to make a decision: let him walk and sign a pardon for both brothers the very day, on live TV; Kim fails to stop him being released and walking out. When the phone rings, Sarah surprises Mahone and escapes- actually he arranged this and has her followed. Kim talks to a grim man in power; Reynolds announces on TV she has a malignant cancer and resigns immediately.

After Michael gets bad news from Lincoln, he sets out to find a prisoner named James Whistler, who holds the key to his freedom. That's easier said than done: James Whistler is hiding in Sona because there's a price on his head, and Lechero is not about to help Michael find him. In addition, both Mahone and Bellick want to get to Whistler too. Meanwhile, T-Bag won't allow a little humiliation stop him from insinuating himself into Lechero's good graces.