International terrorist Charles Rane (Bruce Payne) is about to undergo plastic surgery to change his appearance in order to evade the law. Outside, federal agents and SWAT teams close in to arrest him. It becomes apparent that the plastic surgeon and his staff are in on the plan. Rane becomes suspicious and makes his escape, killing the surgeon in the process. After a harrowing chase through the city streets, Rane is finally apprehended.
Haunted by the shooting death of his wife in a robbery, former police officer John Cutter (Wesley Snipes) has taken a job training flight attendants and security personnel in how to deal with dangerous situations including terrorists. During this particular session, his student is Marti Slayton (Alex Datcher), a flight attendant. When Marti disobeys his instructions, the pair have a brief confrontation.
After class, Cutter sees an old friend, Sly Delvecchio (Tom Sizemore), who is there with a job offer: vice-president for the anti-terrorism unit at Atlantic International Airlines, a major carrier. Cutter is at first reluctant, but Delvecchio and the airline's president (Bruce Greenwood) manage to win him over during lunch.
Cutter boards Atlantic International Flight 163 to Los Angeles... and his new job. By coincidence, one of the flight attendants on this flight happens to be Marti. Also on board is Rane, in FBI custody, headed to Los Angeles to stand trial for his terrorist activities in the past. Several of Rane's people are aboard the plane, disguised as cabin crew and passengers. When Marti performs a head count after boarding is complete, Cutter happens to be passenger number 57.
Mid-flight, Rane is freed when Sabrina Ritchie (Elizabeth Hurley), disguised as a flight attendant, shoots both FBI officers dead. Several other henchmen concurrently spring into action, stealing weapons from the dead officers and taking the plane's passengers hostage. Cutter, in the lavatory during the takeover, emerges and overpowers one of Rane's men. However, Rane responds by executing one of the passengers with a Berreta M9 pistol, making Cutter feel responsible for the man's death. During the confrontation, Cutter and Marti manage to escape, taking the elevator to the plane's lower deck. After a brief fight with one of Rane's men down there, Cutter initiates a fuel dump which forces the Tri Star Lockheed L-1011 to land at a small Louisiana airfield.
Cutter manages to escape from the plane, but Marti is captured by another of Rane's men. On the tarmac, Cutter is quickly apprehended by local sheriff's deputies.
Meanwhile, Rane has made contact with the local sheriff, Chief Biggs (Ernie Lively). Rane promises to release half the hostages in return for fuel and takeoff clearance. Rane also tells Biggs that Cutter is one of his men, a deserter. When the deputies bring Cutter before Chief Biggs, Biggs orders him taken into custody.
As the passengers are being released, Rane and two of his men make their escape. Cutter overpowers the sheriff's deputies, frees himself from his handcuffs, and gives chase on a police motorcycle. Meanwhile, a team of FBI agents arrive, headed by Dwight Henderson (Robert Hooks), who angrily informs Chief Biggs of Cutter's true identity.
At a nearby fair, Cutter manages to kill one of the henchmen and engages Rane in a fight just as police reinforcements arrive. Though back in custody, Rane tells the FBI and police that his remaining team aboard the plane will begin to execute the rest of the hostages if he is not returned to the plane and granted takeoff clearance.
Cutter, Henderson, and Chief Biggs work out a plan for FBI snipers to take down Rane as he boards the plane, upon which FBI teams will storm the plane and deal with his remaining underlings on board. As Rane boards the plane with an FBI escort, Cutter gives the order to fire. However, the sniper bullets hit Rane's FBI escort, not Rane. Rane's second henchman has taken the place of the FBI snipers (who are shown lying unconscious or dead behind him), and he begins firing at the assembled police and agents. He is killed during the gunfight, but not before Rane makes it safely aboard and the plane begins to take off.
With the help of Chief Biggs, Cutter barely manages to get aboard the moving plane via its landing gear. Once aboard, he quickly dispatches Rane's remaining two henchmen, then engages Rane in a prolonged fistfight. Gunfire in the cabin causes explosive cabin decompression, resulting in the main cabin door exploding outward, leaving the cabin open to the sky. As Cutter and Rane continue to fight, they head closer to the open cabin door. Cutter eventually kicks Rane out through the open door, and Rane plunges to his death.
The plane lands safely at the Louisiana airfield for the second time that day. Amid congratulations and celebration, Marti and Cutter make their quiet escape into the distance hand in hand.