It begins with a TV newsman talking about Flight 180 and its survivors and who got killed. Only one person survived, Clear Rivers (Ali Larter).
Then we meet Kimberly (A.J. Cook), who is going on a road trip with her friends.
They start their trip. She is driving with her one girl friend and two stoners in the back. Her dad calls her and tells her that her transmission fluid is low and to get it checked. She says ok and hangs up. Her friend tells her not to stop the car, though, when the warning light comes on. While driving, Kim sees a bus full of rowdy football players, a jocky looking guy, a cyclist, a mom and her son, a truck with logs, a guy drinking in a truck, a stoner, and a cop. Then, when the cop spills his coffee, the truck's cargo falls off. One of the logs goes through his window. The stoner's car flips over the cops, the cyclist falls off and his rammed by his motorcycle, the mom and son blowup, and the stoner gets hit by a truck. Kim's car flips and she thinks all is ok, until she sees the jocky looking guys car on fire. It gets hit by the other truck, which comes for her car, until she wakes up out of a dream.
She pulls over, stopping some people. The cyclist (Eugene), mom and son (Tim and Nora), a pregnant mom, the jock aka lottery winner (Evan), the stoner (Rory), a rich girl (Kat), and the cop (Thomas). He stops and asks Kim why she is blocking traffic. She says that she saw an accident. He doesn't believe her, until the truck passes by. The cars start blowing up. Kim freaks out, Thomas runs to his cop car to alert the other cops, and runs back to save Kim from an oncoming truck, which hits her car, killing her friends. She cries and is taken back to the cop station with the others.
They all talk about how coincidental it is that Kim saw it just like Alex did in the first film. (The highway was Highway 180). Eugene tells everyone about it, how everyone died. Thomas notes that one lived, Clear Rivers. They all talk about how they are going to die, and then leave. Kim's dad arrives and takes her home. She talks to her dad about her mom and all the death stuff.
First, we see Evan, who was a lucky lottery winner and is getting a bunch of messages from women over his money. His microwave blows out as his hand gets stuck in the garbage disposal, after trying to get his ring. He gets out of his apartment right before all of these things start blowing up. He climbs down a ladder, which won't come down, so he forcefully jumps on it, making it fall. He lands on his feet, but slips on some food. The ladder comes down within inches of his head, but after a few gasps, it goes through his eye.
We see Thomas looking up on articles about the Flight 180 incident. He comes upon Alex Browning, the survivor from the first movie, who apparently, while with Clear, was killed by a falling brick. Then we see the other survivors from the car incident, watching the news. Kim sees it and goes to her room. She looks at all her pictures of her friends, looks up Clear Rivers, and goes to the mental institution where Clear is. She talks to Clear, who tells her that she should just save herself, and that all her friends will just die. She feels kind of guilty after Kimberly storms out. She goes home and finds Thomas there. They talk until Kim sees a reflection of pigeons, which scare her. She turns around and sees nothing there. Kimberly deduces that Nora and Tim are going to be attacked by pigeons. We then see Clear in her cell, where she has a sudden change of heart, considering leaving the hospital.
Tim and his mom, Nora, are at the dentist. Tim goes inside. Then the doctor is about to put a needle in his mouth, when a bird hits the window. The dentist says he can't do that with all the distraction, so he gives Tim laughing gas instead. Back in the main room, a fish tank has just begun leaking near a half-pulled out plug. As he is drilling, the dentist hears glass break, and leaves Tim with his mouth open. While Nora and the dentist are trying to get rid of the bird, the plug blows up the circuits. The gas tank turns up all the way. A dangling plastic fish from the ceiling falls into Tim's mouth, who almost chokes until the dentist's aid takes it out. They leave after Tim almost dies. Tim walks near a construction site next to the hospital, while standing under a giant piece of glass.
Some birds come and break the wire, causing it to fall and crush Tim's skull.
Nora cries over the incident. Kim arrives and tries to take Nora away, but Thomas stops her. She says that Nora is next. Then Clear arrives. She takes them to the morgue, where they meet the mortician, William Bludworth. He tells Kim that the only way to stop death is to create new life. She doesn't understand, but this comes to importance later. While at a gas station, Kim has a weird vision, that she is driving a van and it crashes into a river. Thomas then realizes that new life could mean pregnancy. There had been a pregnant lady Isabella stopped before the incident. Thomas sends out an APB on the white van Isabella was driving.
All of the survivors gather at Thomas' apartment. They all talk about who's next, Nora knows it's herself. Kim gives them all cellphones, saying that if Kim sees something, she will call them. Eugene doesn't believe this stuff, so he picks up his jacket, starting for the door. A ball rolls out into a mousetrap. It flings up and knocks down a boat, almost killing Clear. She tells everyone to be careful. Somewhere close by, a cop finds Isabella, the pregnant lady, in the white van, and arrests her for stealing the van, jokingly set up by Thomas.
Nora leaves with Eugene in an elevator. They are with another old man, a guy with a basket full of prosthetic arms. Some of the arms had hands, others had hooks. Back at Thomas', while Rory is securing the potentially deadly things, he knocks down a bunch of stuff. He looks at the ground and sees a shadow of a body and some hooks. Thomas calls Nora, who drops her cell, getting her ponytail caught in the hooks, and tells her that hooks are going to kill her. She doesn't understand, until the hooks trap her hair in the cart. The old man tries to get her free, but the elevator opens and she runs out, only to get her head caught between the doors. The elevator tries to go up and Nora is being choked by the elevator doors, the top of the elevator entrance way, and the floor of the elevator. Kat and Kimberly try to pull her down which cause her to become decapitated. Eugene is scared and crazily goes back to Thomas'. He threatens everyone with a gun and puts to his head, shooting six times, with nothing coming out. He breaks down and cries, while Thomas inspects the gun. It is fully loaded. Kim says it wasn't his turn.
They leave the apartment. Next scene shows the cop that pulled over Isabella putting her in the prison. As they start arguing, Isabella's water breaks. The cop panics and they leave in her van. Back to the others, they are driving. This is where the first movie comes into play. They talk about near death experiences. Eugene explains that he was a teacher, and he was sent to another school. The teacher that took his place died two days later. Kat says that she was in a bus when it killed a girl in the same town Clear was from. It was Terry from the first movie, and the teacher was the one who died in her house. Then Rory says he was in Paris, on acid and all this stuff, when he saw a guy get killed by a falling sign. Thomas says that there had been a train wreck (Seann William Scott's head and Kerr Smith's car from the first film) and that he had been sent to that, while his partner died, where Thomas was supposed to go. Kim just saw on TV that some kid tried to strangle himself in a bathtub. They are all connected to the Flight 180 survivors.
As the cop and Isabella are speeding down the road, Kat's tyre pops and they almost hit Isabella's van. The car goes out of control, and crashes. A log goes through the side, pinning Kat to her seat, and a sharp pole through the back of her headrest. She almost hits it. Eugene has some kind of liver problem and can't breathe. Some farmers arrive and Kim tells them to call 911. He goes to the hospital. A camera crew arrives, only to hit a rock, breaking their gas tank, causing it to leak. Rory hands Kim his wallet and his keys, and asks her to get rid of his porno and drugs,... "anything that would break my mom's heart. Rory then saves the farmer's son from a speeding car. Firemen are using jaws of life to cut off Kat's door. Kat asks the firemen not to do it so loud, the fireman tells her "OK, i'll just put it on quiet mode." Kat replies with "that would be good." The jaws force the airbag to come out, pinning Kat's head against the sharp pole, killing her. The cigarette she was smoking falls in the puddle of gas from the news truck. A tree falls down as Thomas is coming towards Rory. Thomas moves out of the way and lies down. The news truck blows up. A barbed wire cord held by two logs blows away, very gruesomely cutting Rory into several pieces. The farmer lets them take his truck. They leave. Then suddenly Kim starts choking and has a vision of being in the hospital. And a doctor, Dr. Ellen Kalarjian, supposedly choking Isabella. She tells Thomas and Clear what she saw. Then we see Eugene, who is alright until the vents close. A cord connecting to the gas loosens, releasing it everywhere and cutting off Eugene's air supply and the plug is almost disconnected. They arrive. Clear goes to find Eugene and Thomas and Kim go to Isabella.
The baby appears to be choking. Thomas and Kim hear the intercom calling Dr. Kalarjian to Isabella's room. They stop Kalarjian and enter the room. Isabella's baby is fine. Eugene's air comes back from the Emergency battery. They are all celebrating, until Kim has another vision. She sees Isabella at the wreck. But not dead. She wasn't supposed to die in the accident. And then she remembers further and sees bloody hands. Clear then rushes towards Eugene's room. The vents are closed, the gas is still in the room. The plug disconnects sparking a fire that blows up the room, killing Clear and Eugene. Kimberly reaches towards Clear's body, which isn't fully burnt. Thomas pulls her away. She then deduces that the visions are about her. She looks at a wall and sees a newspaper clip, entitled "New Life for Drowning Victim." Kim then sees a white van pull up. She understands what she must do and enters the van, driving into the lake. Thomas follows her and tries to get her out. Everything turns dark as Kimberly sees flashbacks of the characters. She then awakens to see the vision she saw earlier, with Dr. Kalarjian tryin to revive her. Thomas is at her side and welcomes her back to life.
Thomas and Kim are invited to the Farmer's house, the one farmer who called the ambulance for Eugene. They are eating at a barbecue in the back yard. The son goes to check on the food. The father explains that before Rory died, he pulled the farmer's son out of the way of an oncoming truck. Thomas realizes what will happen, and in the background, we see the barbecue blow up, with the son also. The arm lands in the mom's plate and she screams.