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.

With hospitals and clinics under surveillance, Michael brings Lincoln to Nika's home to heal his wounded leg. Then he returns to the place where he parked his Accord and finds that the car has been towed. Meanwhile agent Mahone retrieves Michael's backpack with his passport from a vagrant that broke the rear window of Michael's car to steal the backpack. Michael goes to Brewster Towing yard to recover his car. Meanwhile Sucre finds that Maricruz will marry Hector in a couple of days and he heads to New York in a stolen car. Sara is arrested and her father visits her, pays her bail and orders her to tell a fake version about the incident in Fox River since he will be the next Vice-President of United States. Later she goes to rehabilitation where Kellerman is pretending to be an addicted patient. C-Note schedules a meeting with his wife, but his conversation is bugged by agent Mahone. Bellick and Geary meet each other by chance and later they team-up to get the $400,000 reward for capturing Michael and Lincoln. They go to Fox River and Bellick interrogates Manche Sanchez, who discloses the plan of the fugitives. Michael and Lincoln forge a car accident to escape from Mahone, but they do not see that Bellick and Geary are in their tail.

Michael's plan has hit a snag when the home owner's daughter, a cop, arrives. Mahone argues with Lyle Sands about how to proceed, but ultimately hopes that Tweener, in FBI custody, will reveal the location of the other escapees. Sara is now suspicious of Kellerman, so he tries something different to find Lincoln Burrows. In an Arizona detention facility, L.J. finds out he's to be released the next day; Linc drives to get him. Haywire, in Wisconsin, steals supplies from a camping shop.

In his efforts to try to get hold of all of the money Sucre runs into some unexpected difficulties. And Captain Bellick and his partner have not given up on finding their old inmates.

Michael tries to retrieve an item from Blanding Botanical Garden in Utah, but Mahone's people got to it first. Mahone believes that someone on his team is leaking information to the press; meanwhile Michael does some research on Mahone at an Internet café, then makes a trip to Durango, Colorado, to see a woman there. Linc and L.J. are on the road in Arizona. C-Note is in Chicago, and Agent Lang tries to use his wife to capture him. Bellick and Geary phone C.O. Patterson, at Fox River, to get information on where they should look for T-Bag. Sara is at a motel in Elgin, Illinois, trying to crack Michael's code. T-Bag arrives in Tribune, Kansas, for (as he puts it) "romance". Kellerman is on the trail of Sara.

Captain Bellick tortures T-Bag for the money during which T-Bag swallows the key and Bellick uses dirty tricks to get the key out.Bellick and Mac leave T-Bag on the boundary of the police.Sarah and Michael Scofield meet,but they are constantly chased by Alexander Mahone.Michael gets close to Mahone's helplessness.Meanwhile Lincoln Burrows and LJ are rescued by Lincon's dad but they are still not shielded from the dirty political games. Sucre tries to contact Maricruz but that plan fails because of the state police doing rounds.

Picking up from where we left off, Sucre, Michael, Linc, and Aldo are together, with Mahone on their trail. Sara is face-down in the bathtub as Kellerman prepares to dispose of her body. C-Note is in Harvey, North Dakota with Kacee and Dede, who needs her medication. In Tribune, Kansas, Detective Slattery questions Bellick.

Sara meets Michael and Lincoln in a train station in Evansville, Indiana; when she sees Kellerman with them, she becomes disturbed and upset. Kellerman tells that she has a key of a private cigar club in Chicago. Caroline calls Kellerman and he tells that he is heading to Chicago by train, and she promises his life back, inclusive the chief of staff position. T-Bag tells Susan that they are passing through an "adjustment period" in their lives; when she tells him that she will have a guest called Patty Wallace, T-Bag welcomes Patty with a magnificent family brunch and uses the strong father figure to discipline Zack, seducing the guest with his charm and attitude. Wheeler is reporting the actions of Mahone to the FBI Headquarter and they find that Haywire killed a man in Algoma, Wisconsin. Mahone visits Bellick in River Fox, releases him using a habeas-corpus to make his dirty work, and gives a car, a pistol and an FBI badge to the despicable man. Bellick chases and traps Haywire, and waits for Mahone. In Benson, Minnesota, C-Note and Dede are leaving a snack bar when an addicted thief announces a heist. When Kellerman sees a road block on the train, he realizes that he was betrayed.