This film will start out with an entrance to Williamson High School in Tioga Junction, Pennsylvania. The film enters a 7th grade room, filled with students of kindergarten, 2nd, 7th, and 8th grades.The students' teacher has to go to a meeting, so, Brandon Nichols' mother, Lauren (Mila Kunis) chaperones on the field trip, along with another teacher, Mrs. Vayansky. She walks out to the bus, right when her two other boys, Tristan and Justin, walk into the room. Her grandnephew walks into the room also. Mrs Vayansky walks all the kids down to the bus, where they load on, unknowing that someone filled the whole roof compartment of the bus with snakes. Almost to the Tioga Welcome Center, the snakes are accidentally released by the bus driver while she was smashing a snake with a folder. Many students die, and Mrs. Vayansky dies too. Brandon loses all but 18 students, including himself, and his mom, and brothers and second-cousin. Brandon gathers everything he can to try to kill the snake, but realizes that he has nothing but a folder, a chocolate milk, his iPad and iPod, and 2 pens in his backpack. Carlton Bell sees the pens and says that they can kill the snakes with the ink from the pen, but Brandon realizes that it would be too hard, but Carlton refuses and grabs one of the pens. The bus driver then loses control of the bus and nearly drives the bus off a bridge. Allison Mosher is the only student badly hurt, after breaking her arm. Brandon then gets his iPad out and browses the internet, but a snake creeps onto his lap, and he shoves it into his backpack, and forgets. He then wins tickets to the Super Bowl in Miami, Florida, and then his mom tells him to buy plane tickets. His younger brother Justin asks whose playing the game, but Brandon can't remember, so he tries to figure out what to do next. He decides to count how many died, but is bitten in the leg by a coral snake, and a guaze is wrapped around his leg where the snake bit him. He then realizes the bus is almost to Williamsport, but, the bus driver starts to get real weak, and starts to lose control of the bus. She regains control after the bus swerves into the wrong lane of traffic. Lauren says that they need to find a way to kill the snakes, so Brandon gathers all the people's backpacks, except Chase Austin, who is bitten by a Rattlesnake and dies. When the bus reaches the Lycoming Mall after 10 minutes of cleaning up Chase, the bus driver dies of her injuries. So Lauren has to drive from now on. Brandon decides to put all the dead bodies in the back, but Allison Mosher gets infected by one of the bodies, and gets extremely sick. Brandon gets the first aid kit, but soon sees that it's worthless. Allison then starts throwing up, and Brandon realizes she's not gonna live another hour, so he prepares for her death, and soon enough, she gets attacked by several snakes and dies. Lauren then tells everybody that their gonna be arriving in Harrisburg in about another 3 hours, so they need to keep the bus on the road, but, she gets pulled over by a state trooper, but he dies from an attack while in his car. Lauren finishes the ticket and puts it in her pocket and continues driving. After a while, Brandon's bite starts to get worse, and his leg goes numb, so he asks his mom for help, and she calls Harrisburg's capitol building and asks if they have a hospital with anti-venom, and they end up talking for an hour. During the call, Brandon puts all the dead bodies in the back of the bus. Carlton gets into a fight with Brandon and then ends Lauren's phone call, and she gets mad and starts yelling. They arrive in a town that is getting the worst of a storm, and sees a tornado touch down and everybody gets into a seat and holds on while she pulls over, except Hunter Sackett, who is attacked by snakes and dies. Jared Stermer gets out of his seat, but is killed when the bus is struck by lightning. He was thrown against a seat and he fractured his skull. The tornado roars over, and the bus gets going. Hunter Cass and Andrea Sheive scatter a Burmese Python, and an Anaconda, and the Burmese Python kills Hunter. After that, the scene goes to Harrisburg, 25 minutes later, with Governer Matt Baker discussing with a group of staff about the bus. They take about 10 minutes getting anti-venom for the students who need it. On the bus, Kurtis Strope and Colin Heilbrun are attacked by the same snake in 2 minutes. They each survive. Zoe Skelly is then bitten by a snake, and she too survives. Brandon wonders how all these snakes got onto the bus. And he says that someone must have snuck onto the bus and filled it with snakes to kill a certain amount of people. He then wonders that, because his dad is in prison for abusing his mom, maybe his dad came up with the idea to kill him, his two brothers, and his mom with a bunch of poisonous snakes. He then gets mad and destroys his iPod because it was a gift from his father. He had deleted all the music 3 days earlier on it, so there was no use listening to it. Tristan then gets excited because nnow him, Brandon, and Justin were even because they don't have an iPod. Tristan has a different dad than Brandon, but Justin and Brandon have the same dad. Brandon got the iPod for christmas, but his dad thought Justin wasn't old enough to handle an iPod yet. He then gets into a fight with his mom about his dad and it almost makes Lauren crash the bus. A snake creeps up onto the dashboard, but Lauren kills it. The scene then switches to a Harrisburg hospital distributing anti-venom to Dr. Nathan Bowers (Shia Labouf). After that, he gives the anti-venom to Baker, who keeps it in a briefcase. This takes about 25 minutes, so now the bus is almost to Harrisburg. Everybody notices Harrisburg's Statue of Liberty, and they get distracted from what Brandon was discussing. They then think it's gonna be about another 20 minutes before they arrive in Harrisburg, so they get prepared. Jeremiah Johnston says they need to kill all the snakes, so Brandon gets a battery out of his backpack and plans to short it out and make it explode. They choose Jeremiah to sacrifice himself to save the others. He does so, and the whole bus compartment explodes, and Brandon shoots with his pistol into the fire ball. After that, they conclude that Jeremiah's dead. Brandon and Carlton get into a fist-fight until Lauren shoots the doors to scare them away. Brandon gives one last punch to Carlton, and he breaks his nose. After that they arrive near a huge white building near downtown Harrisburg, and Dr. Bowers and his assistant, Mark Sather (Michael Pena) get hit in the face by the doors because they were jammed. They get everyone off, and whoever needs the anti-venom goes in the ambulance. After that, the film ends, showing what happened in the weeks after.