Handlung

Cameron Poe (Nicholas Cage), a honorably discharged United States Army Ranger, is found guilty of manslaughter in the death of an innocent but drunk bar customer while trying to defend his pregnant wife Tricia (Monica Potter) from him, and sentenced to seven to ten years by a bias judge. During his time in prison, he communicates with his wife and daughter while taking time to better himself.

Eight years later, Poe is released on parole, and is scheduled to be flown back to his hometown in Alabama on the same day as his daughter Casey's seventh birthday. Poe is arranged transport on the "Jailbird", a C-123 airplane, along with a fellow prisoner Mike "Baby-O" O'Dell (Mykelti Williamson) and several other prisoners destined for a new Supermax prison, including William "Billy Bedlam" Bedford (Nick Chinlund), Nathan "Diamond Dog" Jones (Ving Rhames), and Cyrus "The Virus" Grissom (John Malkovich). The prisoner transfer is overseen by U.S. Marshall Vince Larkin (John Cusack); however, he is approached by DEA agent Duncan Malloy (Colm Meaney), who asks to put undercover agent Sims (José Zúñiga) on board the plane in order to gain intelligence from one of the prisoners during flight. Larkin acquiesces but insists the agent go aboard unarmed, but Malloy is able to sneak Sims a gun during the boarding pat-down.

Shortly after the flight takes off, Jones and Grissom are able to free themselves with the help of a distraction by another prisoner, Pinball Parker (Dave Chappelle) faking a seizure, and the prisoners quickly subdue the guards and take control of the cockpit to prevent the pilot from reporting in. In the ensuing chaos, Sims attempts to threaten Grissom, but Poe, recognizing that Sims is at a disadvantage, attempts to talk the agent out of it; Sims ignores the advice and ends up dead. As Grissom organizes the other prisoners to prepare for a scheduled landing in Carson City in order to meet the required prisoner transfer numbers, Poe spots a recording device on Sims' body; he transfers it to one the guards that are being substituted for dead prisoners.

Upon landing to refuel and pick up more prisoners to take them to freedom, Grissom ensures the prison transfer goes smoothly, instructing Pinball to hide the plane's transmitter, and despite Poe's efforts, the plane leaves Carson City without incident. Among the new prisoners boarding are drug lord Francisco Cindino (Jesse Borrego), transvestite serial killer Ramon 'Sally Can't Dance' Martinez (Renoly Santiago), their new pilot, "Swamp Thing" Williams (M. C. Gainey) and cannibal serial killer Garland Greene (Steve Buscemi) known as "The Marietta Mangler".

Poe, along with Jones, go into the hull to determine the cause of the plane's slow speed and find that Parker's body is lodged into the landing wheel compartment, having missed the plane taking off. Poe takes the opportunity to write a message on Parker's shirt to Larkin and pushes the body out of the plane, where it lands in the middle of traffic.

Larkin is quickly made aware of the message; he also discovers the true identity of the "prisoners" dropped off in Carson City, and that plans for the plane's takeover were present in Grissom's cell. He and Malloy realize something is wrong, and while Malloy immediately takes off to follow the plane's transceiver, secretly came aboard a sightseeing plane, Larkin recognizes that the prisoners' plane is headed in the opposite direction to the disused Lerner Airfield; he borrows Malloy's sports-car to make it to the field before the plane can land, calling in the National Guard and other forces to help secure the airfield.

Aboard the plane, Poe attempts to keep his identity secret, killing Bedford when he discovers Poe's parole letter in the personal belongings in the hull. Poe learns from Grissom that this plot was set up by Cindino, promising that once they land at Lerner, another plane will be waiting for them to help them gain asylum in "non-extradition territory".

The plane lands at the airfield, running aground, but no plane seems to be waiting for them; while the rest of the prisoners are forced by Grissom to dig out the plane, Poe explores the field to try to find insulin for O'Dell who is going into a diabetic shock from withdrawal of his medication. Larkin, also on the field, happens upon the plane that Cindino promised, finding that Cindino has double-crossed Grissom and trying to flee on his own. Larkin is able to disable the plane, and the crash alerts Grissom, who shoots Cindino.

The prisoners observe that armed forces are advancing on the field, and they set up an ambush trap for the forces. Larkin and Poe briefly meet to discuss the situation before the troops arrive; Larkin goes off to help stop the troops from being massacred, while Poe returns to the plane to give O'Dell his insulin. As the troops overrun the trap, Grissom and the remaining prisoners return to the plane and take off, despite damage to the plane.

Grissom soon discovers Poe's true identity and after shooting O'Dell, prepares to kill him. Malloy, having tracked down the Jailbird, opens fire on it from a helicopter and disables one of the engines, causing the plane to lose fuel. With Grissom and the others distracted, shooting from the aircraft's ramp, Poe gains control of the cockpit with an improvised hand to hand combat with prisoners in his path and orders not to fire. When Larkin in a second helicopter, tells Malloy about Poe's identity as a parolee, Malloy orders "hold fire" and joins forces. Attempting to land the aircraft to land at McCarran International Airport in Las Vegas, the crippled Jailbird is forced to crash land on "The Strip".

The landing injures the inmates while causing massive destruction along "The Strip" until it comes to a halt in the lobby of the Sands Hotel. Amid the chaos, Poe is thanked by both O'Dell and Bishop for his help. Grissom, Jones, and "Swamp Thing" escape on a fire truck. Larkin and Poe see them trying to flee, pursue them on motorcycles, eventually killing all three escapees. Finally, Poe is able to reunite with his loving wife and daughter, who have been brought by Larkin to meet him.

With all of the convicts apparently dead or recaptured, a croupier at a craps table in one of the Vegas casinos asks a new shooter if he feels lucky. The shooter, Garland Greene (whom is the only prisoner who apparently escaped), takes the dice, sips a margarita and replies without a smile, "Yes, yes he does" and is presumed to be giving up his life as a cannibal serial killer.