Former Army Ranger Cameron Poe (Cage) is sentenced to 10 years in prison for manslaughter for using excessive force on a drunk man while trying to protect his pregnant wife Tricia. Poe is paroled eight years later, and is to be released after being flown to Alabama on the Jailbird, a C-123K transport prison aircraft. Along with Poe are several other prisoners including his diabetic cellmate and friend Mike “Baby-O” O’Dell, who is being transferred (but not yet paroled) with Poe. The transfer is being overseen by U.S. Marshal Vince Larkin (Cusack), as the transfer includes notorious criminal mastermind Cyrus “Cyrus The Virus” Grissom, gangster and Black Guerrilla member Nathan “Diamond Dog” Jones and mass murderer William “Billy Bedlam” Bedford for their transfer to a new Supermax prison. Larkin is approached at the last minute by DEA agents Duncan Malloy and Willie Sims, who ask for Sims to be brought aboard disguised as a prisoner so that he can extract more information from drug lord Francisco Cindino, a prisoner that is to be picked up at Carson City, Nevada en route. Larkin agrees, unaware that Malloy has hidden a gun on Sims’ body. As the Jailbird takes off, another prisoner Joe “Pinball” Parker incites a riot, allowing him to set free Diamond Dog and Grissom. Cyrus quickly rushes to the cockpit, killing the co-pilot and forcing the pilot to continue to fly the aircraft. Cyrus then announces the prisoners’ takeover of the Jailbird and takes the prison guards hostage. Sims attempts to control the situation with his weapon, but Cyrus shoots him first. Poe feigns cooperation with the other prisoners as they prepare to offload guards disguised as prisoners at Carson City; Poe is able to sneak a recording device Sims had onto one of the now tied up guards. The transfer proceeds, among the new prisoners are Cindino, pilot “Swamp Thing” Williams, and serial killer Garland Greene, whose murders make “The Manson family look like the Partridge family”. Pinball takes the aircraft’s transponder and plants it on a small sightseeing aircraft. Jailbird takes off before the recording device can be found, but soon afterward Larkin and Malloy are alerted to the situation, after other prison guards recognise the tied up guards. Malloy berates Larkin for assigning incompetent guards to the transport aircraft and then chases off after the transponder, while Larkin discovers information in Grissom’s cell that indicates this escape attempt has been planned with Cindino. On the Jailbird, Grissom reveals that they will be going to the small Lerner Airfield where Cindino has arranged passage for them all to a non-extradition country. Poe finds Pinball’s body stuck in the landing gear, the convict not having made it back in time, and secretly writes a message to Larkin about Lerner Airfield before pushing it out of the aircraft. The body lands in the middle of Fresno, California, and Larkin is alerted, ordering the National Guard there while he drives there himself in Malloy’s sports car. Billy Bedlam discovers Poe’s true identity after going through his personal possessions, identifying him as a parolee and former Ranger, and Poe is forced to kill Bedlam when he charges at Poe. At Lerner, the aircraft overruns the small runway. There is no immediate sign of Cindino’s aircraft and Grissom orders the prisoners to start to dig out the Jailbird. Poe uses the time to locate insulin shots for O’Dell, and happens upon Larkin. The two quickly brief each other on the situation as Poe has to return before suspicion is raised. Larkin encounters Cindino with his agents preparing a small jet for departure and is able to sabotage it on takeoff. Grissom realizes Cindino had tricked him and kills him by burning him with the aircraft as it explodes. Meanwhile, one of the convicts, assigned to watch for trouble, spots the approaching National Guard and alerts the others. The prisoners equip themselves with assault rifles in the aircraft that were originally intended for corrections officers and prepare to massacre the troops in an aircraft graveyard. However, Larkin is able to save most of the troops using a bulldozer as a bullet shield, forcing the prisoners to retreat to the Jailbird and prepare for take off. Poe, after giving O’Dell his shots, tries to escape with him and a female guard who had been protecting herself from serial rapist Johnny “Johnny 23” Baca aboard, but the aircraft has taken off by the time they are ready. Poe’s identity and true intent is revealed to the prisoners when Diamond Dog discovers Billy Bedlam’s corpse and Poe’s possessions. As Grissom is about to kill Poe, Malloy arrives with Bell AH-1 Cobra assault helicopters and fire upon the Jailbird, damaging its engines and draining its fuel tank. Swamp Thing is forced to crash-land the aircraft in the only open paved surface nearby, the Las Vegas Strip. The aircraft causes a great deal of destruction as it skids to a stop in front of the casino, creating a mass of chaos that allows Grissom, Diamond Dog and Swamp Thing the opportunity to escape on a fire truck while Las Vegas police secure the area and apprehended the prisoners. Poe and Larkin team up to chase down the three, believing they have killed all three after a high-speed chase. Poe thanks Larkin and tells him he is now someone whom he can trust, and then goes to reunite with Tricia and his daughter whom he has never met. Garland Greene’s fate after the crash is revealed: he is now a free man, and was seen gambling and drinking while on a winning streak at a casino, although it is not known whether the police later apprehend him.