It is the morning after their escape from Fox River, and the inmates narrowly avoid being caught by Bellick as they jump onto a freight train. FBI Special Agent Alex Mahone has been assigned to their case and calls a press conference urging the public to turn in the "Fox River 8." Michael, Lincoln, Abruzzi, C-Note, and Sucre encounter a hunter and his daughter. He holds them at gunpoint until Abruzzi grabs the daughter and forces the hunter to give them his SUV and let them go. The escapees head for a location where Michael has things stored. Agent Mahone tracks Michael's credit card to a storage facility in Oswego, but quickly figures out that one of Michael's tattoos holds the real location. Michael's tattoo "Ripe Chance Woods" is a clue pointing to a cemetery where Michael has items buried in the grave of "E. Chance Woods." Just two steps behind, Agent Mahone arrives at the scene just as the inmates have gathered what they need. In the meantime, T-Bag discovers a veterinary clinic and forces the Vet to re-attach his severed hand. Dr. Sarah Tancredi recovers from her overdose. Inside her purse, she finds an origami swan left for her by Michael with a message, "There's a plan to make all of this right", and a code. The code is a series of numbers which reads 3221243324 for the first line, 4221312231 for the second, and 23133121 for the third. Veronica locates Terrance Steadman in Montana, and finds that the doors are locked from the outside, holding him hostage (albeit willingly). Veronica calls 911, and then talks to Lincoln and tells him what she has learned. Employees of The Company arrive and kill Veronica for having unraveled their plot and for having found Steadman. Lincoln hears Veronica's final words as she dies, and is consumed with grief. Mahone studies Michael's tattoos, and feels that they are the key to finding the escapees.

Linc and Michael have decided to take the keys and escape, figuring at least they'll go down fighting. FBI Special Agent Alexander Mahone chased them while staying in contact with Secret Service Special Agent Paul Kellerman who suddenly shot Mahone and gave the brothers a ride because he wants revenge on the White House; Linc wants his instead, but is offered the location of Terence Steadman. T-bag visits his ex-girlfriend, who tells him the children think he's their Uncle Teddy on an oil rig, but he moves in; when she goes for a gun, he attacks her and her son attacks Zach him, so he turns the home into a private prison. In prison, former boss Bellick, who naively had made a deal in order to do his time in Illinois, shivers in general population among the prisoners he abused and their mates, he has none as the new warden sees him as an example of his new, clean ship; he soon realizes there's no pleasing them, and tries hitting hard; a loyal guard warns him the night shift is on his enemies side as he treated them badly. Benjamin Miles 'C-Note' Franklin tries to save his Kacee who is in custody, advising her to put all the blame on him; after hearing how scared his girl is, he asks one of his friends for help to run while she's on bail but the judge refuses bail. Mahone awakes in hospital, and reports to Kim on Kellerman's betrayal and the brothers' escape, which is hitting the TV news, but refuses to play anymore, even if that means jail; when his wife Pam phones their son is hurt he rushes out for Colorado, but is stopped to hear it's a warning to force him back in line; however he is through doing Kim's bidding and shoots his man. Kim calls Steadman's bodyguards: he must be evacuated to a safe house as Kellerman knows his residence, but he is already there with the brothers- Kims orders to kill everyone, but only the FBI men are shot; Kellerman explains Steadman is made unrecognizable, including plastic surgery, so their only option is to get him to Washington, where FBI agents who know can still make the truth stick. Michael decides instead to turn himself in while informing the press, despite Kellermans gun aimed at him, but Steadman prefers to commit suicide, and his corpse is worthless for the brothers.

In Cutback, Montana, Kellerman lures the police and Michael and Lincoln abduct the cameraman Greg of Fox News and succeed in escaping from the siege. Michael and Lincoln decide to tape a message to be released in the Breaking News. Mahone is back in Chicago and analyzing the message; he interrogates Greg and he tells that he had overheard Michael tell that they should cover 460 miles in six hours. Mahone deduces that they intend to meet President Caroline in Denver. Wheeler discusses with Mahone and yells that the Internal Affairs department asked him to follow all moves of Mahone. Bellick is badly wounded in the infirmary of Fox River. Sucre befriends an old passenger in a bus to Ixtapa; however the driver asks him to leave the bus in a small town and Sucre robs the Volkswagen of the old man. In Algoma, Winsconsin, Haywire befriends a young couple and the girl has bruises on her arm; she tells that her abusive drunken father beat her.

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.