Ex-Army Ranger Cameron Poe is sentenced to prison for manslaughter after defending his wife in a bar brawl. Eight years later, Poe is paroled and is set to be released, eagerly anticipating the chance to meet his daughter for the first time. His journey home is aboard the Jailbird, a transport plane filled with some of the nation’s most dangerous criminals. The felons are being transferred to a new supermax facility, and among them are notorious criminal mastermind Cyrus "The Virus" Grissom and his henchman Diamond Dog. Unbeknownst to the authorities, the convicts have hatched a sophisticated escape plan.

Mid-flight, the prisoners manage to seize control of the plane, with Cyrus orchestrating the takeover. Poe finds himself caught in the middle, playing a delicate game in order to protect his friend and parolee, Mike "Baby-O" O'Dell, who is diabetic and in need of his medication, which is onboard the plane. Furthermore, Poe covertly attempts to thwart the felons' plans and protect the female guard, who is at the mercy of the inmates. On the ground, U.S. Marshal Vince Larkin senses that something is amiss and becomes suspicious of the flight, leading him to investigate. As the convicts redirect the plane and begin executing their escape, Larkin and Poe's covert resistance intersect, setting in motion an intense cat-and-mouse game in the skies and on the ground.