One year after the first film, college student Kimberly Corman is headed to Daytona Beach, Florida for spring break with her friends, Shaina McKlank, Dano Estevez, and Frankie Whitman. En route, Kimberly has a premonition of logs falling off a semi, causing a massive car crash that kills everyone involved. She stalls her car on the entrance ramp, preventing several people from entering the highway, including Lottery winner Evan Lewis; widow Nora Carpenter and her fifteen-year-old son Tim; businesswoman Kat Jennings; stoner Rory Peters; pregnant Isabella Hudson; high school teacher Eugene Dix; and Deputy Marshal Thomas Burke. While Thomas questions Kimberly, the pileup occurs. Shaina, Dano and Frankie are killed by a speeding truck, but Kimberly is saved by Thomas.
The survivors are brought to the police station, where they learn about the curse of Flight 180. Later, a chain reaction causes a fire in Evan's apartment which he barely escapes; but when Evan slips the escape ladder falls and impales his eye. Thomas researches the survivors of Flight 180, and discovers that Alex Browning was killed by a falling brick. Kimberly visits Clear Rivers, the last survivor of Flight 180, who is now a voluntary inmate at a psychiatric ward. Clear refuses to help, but while arguing with Kimberly realizes that the survivors are dying in reverse, and warns Kimberly to look out for "signs" of Death. Upon arriving home, Kimberly has a vision of a flock of pigeons attacking her and she and Thomas rush to save Nora and Tim, but they arrive too late and Tim is crushed by a glass pane at a dentist. Clear decides to help and introduces Kimberly Thomas to mortician William Bludworth, who tells them that only "new life" can defeat Death. They believe that if Isabella has her baby it will ruin Death's plan and they will all be safe.
Isabella is accused of driving a stolen van and taken into custody, while the other survivors reunite for safety. After Nora is decapitated by malfunctioning elevator doors, the group leaves to find Isabella, who has gone into labor at the police station, while the policeman on duty rushes Isabella to the hospital in her van. Along the way they discover they have all cheated death twice; had it not been for the survivors of Flight 180 they would all be dead, which explains why the survivors are dying in reverse. Since Thomas saved Kimberly from being hit by the truck, she is last on Death's list.
The survivors' vehicle suffers a blowout, prompting them to swerve onto a farm. The back of the car is penetrated by PVC pipes which injure Eugene, and he is rushed to the hospital. As rescuers arrive at the scene, Brian Gibbons, the son of a farm owner, is nearly killed by a speeding news van, but Rory saves him. Using the Jaws of Life Kat's rescuer accidentally activates the airbag and her head is impaled by a pipe protruding from her headrest. Her cigarette falls out of her hand and into a gasoline leak leading to the news van, causing the van to explode, and sending a barbed wire fence flying through the air, which kills Rory.
Kimberly, Clear and Thomas rush to the hospital, and Kimberly has another vision of Dr. Ellen Kalarjian "strangling" Isabella. After Thomas immobilizes Dr. Kalarjian, Kimberly and Thomas witness Isabella give birth and assume they have cheated death. However, Kimberly has another vision of someone with bloody hands in a submerging van and realizes that Isabella was never meant to die in the pile-up.
Clear searches for Eugene, but accidentally causes his room to explode from an oxygen combustion, killing them both. Kimberly realizes the person in her vision was herself and immerses a van in a lake to drown herself. Kimberly is rescued by Thomas and resuscitated by Kalarjian, which was her actual premonition, granting her new life. Sometime later, Kimberly and Thomas have a picnic with Brian's family and Kimberly's father to celebrate their survival. There they learn of Brian's deterrence from Death when his father tells them he was almost hit by a van, but Rory saved him. The group then see a malfunctioning barbecue grill explode, killing Brian.

Question: What do they discover on the way to reunite for safety?
Answer: They have all cheated death twice.