Picking up eight hours after their escape from Fox River, Michael, Lincoln, Sucre, Abruzzi and C-Note are on the run for their lives as a vengeful Bellick leads the prison guards seeking to capture their escaped quarry; Dr. Sara is in critical condition from her overdose; Veronica finds herself a prisoner with Terrance; T-Bag tries to get the upper hand while fleeing from the authorities; and a new take-charge FBI investigator proves to be Scofield's match.
Mahone tries to lure the escapees by targeting an imprisoned LJ. Michael and Lincoln come up with a plan to free LJ from jail. Sucre, Abruzzi and C-Note have a plan of their own, but only to break free of their pursuers.Meanwhile, Bellick and Warden Pope feel the heat following their unsuccessful attempts to capture the escapees.Tweener infiltrates a bunch of college students on their way to spring break.
Mahone zeroes in on Michael and Linc's car, which was towed to a Chicago lot, but Michael gets there first. Unfortunately for the brothers, the backpack containing their fake IDs isn't in the vehicle. Elsewhere, Sara is released from the hospital, but that's not good news, especially after a difficult meeting with her father; Sucre and C-Note are determined to get to their loved ones, no matter what; and Bellick and Geary go into the bounty-hunting business together.
Bellick and Geary catch up to Michael and Lincoln. Abruzzi surfaces in Brooklyn with plans to flee to Sardinia, but first makes a side trip to D.C.
T-Bag stops at a gas station, where his vehicle attracts attention. Tweener and Debra Jean hit it off as they head off to Utah, and Kellerman strikes up a conversation with Sara after the NA meeting.
Michael and Lincoln search for Westmoreland's hidden money in Tooele, Utah. Sucre goes to Las Vegas to stop Maricruz from marrying Hector. Maricruz's sister tells Sucre she'll arrange for the two of them to be alone together, but instead calls the cops. Mahone picks up an interest in the legend of D.B. Cooper and then receives a mysterious package. Kellerman gets one step closer to Sara.
Michael and Lincoln go house-hunting in Utah to find Westmoreland's hidden money; T-Bag shows his particular brand of Southern hospitality; Haywire finally re-surfaces; Sucre finds a familiar face on the road; Mahone's interest in the legend of DB Cooper leads him closer to the escapees.
Michael, Sucre, T-Bag and C-Note claim the hidden treasure.An anxious Lincoln risks everything to get to LJ. LJ grows wary about the easy getaway. Kellerman rethinks where his loyalties lie after Sara gets to The Company's hit list. Mahone results to deadly force to get the truth out of Tweener.
The fugitives again split up as they scurry out of Tooele, but only one has the money. Later, Bellick and Geary arrive and question Jeanette Owens. In Arizona, Linc watches as LJ is freed from lockup. And in Chicago, a Reynolds thug barges in on Sara, while Mahone must answer for the deaths of Abruzzi and Tweener.
Michael looks up Mahone's ex-wife and discovers something telling about his pursuer. And Sara figures out what the numbers on the origami birds mean, learning where to meet Michael in the process. Trouble is, so do Kellerman and Mahone. Linc and LJ head for the rendezvous point, too. Meanwhile, C-Note returns to Chicago for a rendezvous with Kacee and Dede, but Lang gets to them first; and T-Bag seeks out Ms. Hollander, but stops first to buy some flowers.
Michael and Sara find each other in New Mexico, but Mahone finds them both. In Arizona, Lincoln and LJ get into another auto wreck. And in Nebraska, Sucre tries desperately to get in touch with Maricruz by phone.
While Michael makes his way to a rendezvous with the plane and, he hopes, Lincoln, Mahone remains in the factory where Michael left him, but not for long. Meanwhile, Linc has to say good-bye to LJ again; Sara is in a tight spot, and T-Bag gets out of one, but he leaves something behind.
With Mahone on their trail, Michael, Lincoln, their father, and Sucre make a run for the getaway plane. Michael's reunion with his father sheds light on his difficult childhood.The women in Bellick and Kellerman's lives coerce their men to confess their sins.A medical emergency forces C-Note to risk it all.
Mahone catches up with Michael and Linc, but the border patrol arrives at the scene before he can shoot them. This is bad news for Mahone and Kim, but not for Kellerman. Meanwhile, T-Bag needs a new hand as he searches for Ms. Hollander, and he finds other female companionship; Bellick is denied bail and is running out of options, as is Sara; and Sucre must take a leap of faith when the Feds lock on to the plane carrying him to Mexico.
Lincoln and Michael are on the run with Kellerman as they figure out how to take the fight back to "The Company". Meanwhile an injured Agent Mahone decides he's done working for "The Company" but his decision has bad repercussions. Back at the prison, Bellick gets a taste of the medicine he gave out when he was the Captain.
Michael, Lincoln and Kellerman take the airwaves hostage as they attempt to evade the authorities and get a message to a missing Sara; Bellick gets a surprise visit in Fox River's infirmary; Haywire resurfaces and lands in more trouble; Sucre takes his good Samaritan for a ride
C-Note gets into a tricky situation when a robber holds up the diner he is in and demands every-one into the storage room until the police arrive.Michael, Lincoln and Kellerman get closer to revealing the conspiracy with the help of Sarah.Mahone finds a new ally in Bellick.
Michael and Sara realize that Warden Pope is the key to recovering information that will bring down The Company; Mahone corners another escapee; C-Note fears for his daughters life; Sucre learns the dangers of hitchhiking en route to reuniting with Maricruz; and T-Bag walks down memory lane when he takes the Hollander family to his childhood home.
T-Bag digs deep and finds his 'nice-side' with the help of a psychiatrist. Michael, Lincoln, and Sarah get their hands on evidence needed to bring down The Company, while Kellerman is close to finding the President.
As Kellerman prepares for an assassination, Michael is determined to confront the President and expose her secrets recorded on the audiotape. Mahone plays a tense waiting game with Sarah. T-Bag's lost luggage may prove a windfall for Bellick and Sucre. C-Note's drastic actions leave him hanging.
Sarah weighs sacrificing herself in order for Michael and Lincoln to set sail to freedom; T-Bags reign of terror continues south of the border as Bellick forces Sucre to track down the missing money; Mahones actions finally catch up with him; and an escapee finally tastes freedom.
The day has finally come for Sara's trial while critical information that will exonerate her is being debunked. Meanwhile, Michael is determined to get his hands on the 5 million and to stop T-Bag's reign of terror. Bellick is also money hungry and will do whatever it takes to hunt down T-Bag. Kellerman decides his fate while Lincoln and Mahone square off.
Michael tries to save his brother and himself from the unstoppable Mahone. Kellerman's testimony at Sarah's trial proves different from what was expected, could this be the end for Sarah? Sucre puts everything on the line to save his Maricruz. Just like old times, T-Bag and Bellick are at it again but this time there will be a winner.