In the township of Ft. Chicken, Illinois, a fourth grade student at Ft. Chicken Elementary, Shelly Linker (Sunny May Allison), consumes a tainted chicken nugget covered in black splotches. Elsewhere, wannabe horror writer Clint Hadson (Elijah Wood) substitutes at Ft. Chicken Elementary, where he reunites with his former high school crush, Lucy McCormick, (Alison Pill), but discovers she is dating Wade Johnson (Rainn Wilson), the PE teacher. During class, Shelly, who had been experiencing numerous symptoms, brutally attacks her classmate, Patriot (Cooper Roth) after he tugs on one of her pigtails only to have it torn out of her scalp. She bites his cheek, infecting him with the virus; she also claws Clint, but he appears to show no symptoms. Though she tries to escape the school ground before she fully turns, Shelly turns feral and spreads the infection throughout the school, resulting in the other children becoming infected and attacking the school staff; Mr. Pederson, Miss Nash, Mrs. Gordon, Nurse Rhonda, Vice Principal Simms and Mr. Henderson are all killed by the children. The few surviving staff members, consisting of Clint, Lucy, Wade, Tracy Lacey (Jack McBrayer), Rebbekah Halverson (Nasim Pedrad), Doug (Leigh Whannell), and Mrs. Birk (Tammie Baird), hide in the faculty lounge but are attacked by Patriot who tackles Mrs. Birk into a cupboard and mauls her to death (Tracy, apparently unaware of her real name, screams “Who is that lady?!” when this happens). After escaping with an uninfected student, Calvin, the staff barricade themselves in the music room, but are discovered by Shelly. A police officer (Matt Jones) arrives at the scene to calm down the children, not realizing that they are beyond help, but has two fingers bitten off and is then mauled by Shelly as she escapes the playground and hides in his car. Wade notices Clint has been infected by Shelly and quarantines him, but Doug deduces that the virus doesn’t affect him like it does the children. The staff decide to wait until the parents arrive to pick up the children, but this plan fails when Racer Dopkins, son of the local PTA president, infects his baby brother and the zombified baby attacks and kills his oblivious mother. They manage to rescue another child, Tamra (Morgan Lily), but discover she has also been infected. The staff are attacked by the children again, and Wade kills Dink (Miles Elliot), one of the infected children, by beating him to death with a fire extinguisher. Doug analyzes his brain, which has turned black and rotten due to decomposition, and realizes that the virus is only dangerous to the prepubescent (not going through puberty), which is why Clint and Tamra didn’t turn feral as they had passed that stage. The staff and uninfected children unite with the janitor Mr. Hitachi (Peter Kwong), but Calvin passes out due to diabetic shock. The group opts to send Clint through the ventilation system to gather a chocolate bar for Calvin, Wade’s truck keys, and their cellphones. Lucy joins Clint and the two confess their feelings to each other while trapped in the library. Wade also apologizes for his behavior over a walky-talky. Though they discover the cellphones to have been destroyed by Patriot, they manage to secure a chocolate bar and revive Calvin. The group then reunites after Clint knocks out several children with drugs and, utilizing various tools in the school as weapons, battles the children on the playground and manages to escape. However, Mr. Hitachi and Wade are seemingly killed by the children. After killing a stowaway Patriot by crushing him against a tree, the group arrive in the nearby town of Danville, only to discover it has been similarly overrun by the infected children. The group realizes that the infection has spread across the United States, with schools burning to the ground and reports of violence and destruction caused by children, and they are attacked by a horde of infected children. They barricade themselves inside a funhouse and manage to retrieve a chicken nugget contaminated with the virus, which Doug will use to possibly make a vaccination for the virus, but discover that the infected children, including Shelly, are inside the funhouse. However, Wade and Mr. Hatachi arrive and rescue the group, setting the infected children on fire with gasoline. They then escape in crossing guard Rick’s (Jorge Garcia) van, driving out of the town to “someplace kids don’t wanna go”. They are briefly pursued by a flaming Shelly, but she falls down and burns to death. In the post-credits scene, the janitor is sitting wielding a machete and finishes the frog and caterpillar story.