On May 13, 2000, high school student Alex Browning boards Volée Airlines Boeing 747 Flight 180 with his classmates for their senior trip to Paris Charles de Gaulle Airport from New York John F. Kennedy Airport. Before takeoff, Alex has a premonition that the plane will explode in mid-air, killing everybody on board. When the events from his vision begin to repeat themselves in reality, he panics and a fight breaks out between Alex and his rival, Carter Horton. As a result, several passengers are removed from the plane, including Alex, Carter, Alex’s best friend Tod Waggner, Carter’s girlfriend Terry Chaney, teacher Valerie Lewton, and students Billy Hitchcock and Clear Rivers. None of the passengers, except for Clear, believes Alex about his vision until the plane explodes on takeoff, killing the remaining passengers on board. Afterward, the survivors are interrogated by two FBI agents, who believe that Alex had something to do with the explosion.
Thirty-nine days later, the survivors attend a memorial service for the victims. That night, an unusual chain reaction causes Tod to be strangled to death in his shower. His death is deemed a suicide, but Alex does not believe that Tod killed himself. He and Clear sneak into the funeral home to see Tod’s body, where they meet mortician William Bludworth. He tells them that they have cheated Death’s plan and Death is now taking the lives of those who were meant to die on the plane.
The next day, Alex and Clear discuss what the mortician said at a café. Although Clear is skeptical, Alex believes that they can cheat Death again if they look out for omens. They encounter the rest of the survivors and, when Carter provokes Alex, Terry berates him before storming off in anger and getting run over by a speeding bus.
After watching a news report on the cause of the explosion, Alex realizes that the survivors are dying in the order they were meant to die on the plane. He deduces that Ms. Lewton is next and rushes to her house to ensure her safety. Thinking Alex is up to no good, Ms. Lewton calls the FBI agents, who bring him in for questioning. Although Alex is unable to convince the agents of what is happening, they decide to let him go. Nonetheless, he is too late to save Ms. Lewton, whose house explodes after she is impaled by a falling kitchen knife.
The remaining survivors reunite and discuss what to do while driving through town. During the conversation, Carter learns he is next on Death’s list. Frustrated over not having control over his life, Carter stops his car on railroad tracks, wanting to die on his own terms. He changes his mind at the last minute but cannot get out when his seatbelt jams. Alex manages to save Carter just before the car is smashed by an oncoming train, and Billy is decapitated by flying shrapnel. Alex deduces that, because he intervened, Death skipped Carter and moved on to Billy, and he realizes he is next on Death’s list.
Later, while hiding out in a fortified cabin, Alex recalls changing seats with two girls in his premonition, meaning Clear is actually next, and he rushes to save her while being chased by the agents. Meanwhile, Clear is stuck inside her car with a leaking gas tank, surrounded by loose electrical cables. Alex arrives at her house just in time and grabs the cable, allowing her to escape from the car just before it explodes.
Six months later, Alex, Clear, and Carter travel to Paris to celebrate their survival. While discussing their ordeal, Alex realizes that Death never skipped him. After seeing more omens, he leaves the table, and a bus almost hits him, but it swerves and crashes into a large neon sign that swings down towards Alex. Carter pushes Alex out of the way at the last second, and Alex says that Death has skipped him. When Carter asks who is next, the sign swings back down towards Carter, and the screen cuts to black followed by a loud smash, leaving Alex and Clear as the last survivors of Flight 180.