Cameron Poe, portrayed by Nicolas Cage, is an honorably discharged U.S. Army Ranger who finds himself facing a manslaughter charge after a tragic incident where he kills an intoxicated man to defend his pregnant wife, Tricia. Convicted by a biased judge, he is sentenced to a long prison term of seven to ten years. While incarcerated, Poe keeps in touch with his beloved wife and daughter, striving to better himself during his confinement.
After eight long years behind bars, Poe is paroled and is set to return home just in time for his daughter Casey's seventh birthday. However, his journey back to Alabama is anything but ordinary; he boards a C-123 airplane known as the "Jailbird," accompanied by fellow inmate Mike "Baby-O" O'Dell and a group of notorious prisoners, including the cunning Cyrus "The Virus" Grissom played by John Malkovich, and Nathan "Diamond Dog" Jones.
The seemingly straightforward prisoner transfer is overseen by U.S. Marshall Vince Larkin, portrayed by John Cusack. Shortly before takeoff, Larkin receives a request from DEA agent Duncan Malloy to place an undercover agent on the flight for intelligence purposes. Ignoring Larkin's insistence on safety, Malloy manages to smuggle a firearm onboard, setting the stage for chaos.
Once airborne, the criminals spring into action, using a distraction from a fellow inmate to overpower the guards and seize control of the plane. In the ensuing mayhem, Sims, the undercover agent, finds himself in a life-or-death situation. Despite Poe's attempt to dissuade him, Sims meets a grim fate, prompting Poe to take action himself by discreetly transferring evidence of their plot to a fallen guard.
Upon landing for a refueling stop, the plot thickens when new inmates, including drug lord Francisco Cindino and serial killer Ramon 'Sally Can't Dance' Martinez, join the flight. As the unanticipated developments unfold, Poe discovers that one of their own is ensnared in the tragedy when a fellow inmate’s body becomes lodged in the plane’s landing gear compartment. Despite the obstacles, Poe carefully crafts a message to Larkin pleading for help.
As Larkin uncovers the sinister turn of events, he races against time, coordinating military support at a deserted airfield where the convicts intend to escape. With tensions high aboard the plane, conspiracy and betrayal abound, leading to shocking confrontations as Poe’s quest for freedom turns into a fight for survival.
Grissom’s schemes unravel as Cindino's treachery comes to light, resulting in deadly confrontations. Amid the chaos, Poe demonstrates resilience and bravery, risking his life to save a fellow inmate while avoiding a disastrous fate. The film culminates in a high-octane showdown as Poe confronts Grissom and fights to reclaim his freedom.
With the plane crash-landing on the iconic Las Vegas Strip, amidst injuries and destruction, Poe finally reunites with Tricia and Casey, savoring the culmination of his tumultuous journey. Meanwhile, the enigmatic Garland Greene, the only convict presumed to have escaped, stirs intrigue as he calmly accepts his next roll of the dice, leaving an air of unpredictability lingering in the aftermath of the chaos.
