Original channel: FOX
Country of origin: United States
Original present: 2006
Genre: Drama, Thriller, Action
Created by Paul Scheuring
Language: English

Season 2 (22 episodes) begins eight hours after the escape, focusing mainly on the escapees. Series creator Paul Scheuring describes the second season as "The Fugitive times eight" and likens it to the "second half of The Great Escape". The fugitives split up and journey to locations across the country with the authorities close behind them as they each pursue their individual goals. Brad Bellick (Wade Williams) gets fired from the prison where he worked as a guard in season 1 and chases after the inmates himself for the reward money . Several of the escapees reunite in search of a large cache of money buried long ago by another prisoner who is rumored to be D. B. Cooper. T-Bag manages to escape with the money, and the brothers spend the rest of the season tracking him down, both for the money which they need to escape the country, and because Scofield feels responsible for releasing the murderer.

Federal agent Alexander Mahone (William Fichtner) is assigned to track down and capture the eight fugitives, but is revealed to be working for The Company; The group wants all eight men - especially Lincoln - dead. Several of the escapees are killed or recaptured, but the brothers make it to Panama. During the brothers' flight, Sara's father, Governor Frank Tancredi, is murdered because he discovers the truth behind Lincoln's innocence. After discovering him dead, Sara returns to her apartment only to have to flee for her life. She meets up with Michael on two different occasions, remaining with him as the brothers try to bring down the current President, a Company member. To ensure the brothers' safety, Sara allows herself to be arrested and faces a trial. During the trial, the testimony of former Secret Service agent Paul Kellerman, who used to work for the Company-controlled President, exonerates Lincoln and Sara. Meanwhile Michael, T-Bag and Mahone are arrested by the Panamanian authorities and are imprisoned at the Penitenciaría Federal de Sona where they find Bellick who had been arrested earlier that episode.