The story continues eight hours after the prison escape from Fox River State Penitentiary, focusing mainly on the escapees. New characters are introduced, including a federal agent Alexander Mahone (William Fichtner), who is assigned to track down and capture the eight escapees. The fugitives journey to locations across America with the authorities close behind them as they each pursue their individual goals. Meanwhile, the conspiracy plot develops as "The Company" continues their plan to locate and eliminate Lincoln Burrows and others who get in their way. Much of the storyline concerning the conspiracy concludes by the season finale.

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