Fifty years ago in the planned community of Seabrook, an accident at the Seabrook Power Plant resulted in an explosion that caused half the population of Seabrook to turn into brain-eating zombies. Those that weren't affected constructed a wall to quarantine the zombies from the rest of Seabrook in a territory called Zombietown. The government later created bracelets for zombies, called Z-Bands, that deliver soothing electromagnetic pulses to keep zombies from craving brains. In the present day, zombie students from Zombietown transfer to the human high school, Seabrook High, where suburban life is filled with uniformity, traditions, and pep rallies. The zombies in the school are patrolled by Dale, whose daughter Addison and nephew Bucky are on the school's cheerleading team.

Addison begins a relationship with a zombie student named Zed, who is an exceptional player on the school's football team due to his Z-Band being hacked by Eliza, one of his zombie friends. Addison and Zed's relationship is initially unknown to all of the students and staff except two of Zed's zombie friends, Eliza and Bonzo. Bucky, who leads the cheerleading team, is jealous of Zed's popularity and makes sure Addison isn't able to meet him. Addison is invited by Zed to attend the zombie party in Zombietown. She attends and has a private moment with Zed in the "zombie park". Just before the pair can kiss, however, the Zombie Patrol crashes the party and takes away Addison. At home, Dale and his wife Missy, the mayor of Seabrook, find out that she has a new crush and advise her not to do any cheering until they know who it is, not knowing that the crush is a zombie. The next day, Zed shows up on Addison's doorstep looking human. He and Addison leave her house and go on a date, where he admits he's been messing with his Z-band. Addison tells him that it is the others that have to change, not him.

On the day of the homecoming game, Bucky finds out about Zed's Z-Band hack and has his followers Stacey, Tracey and Lacey steal Eliza's laptop to hack the Z-Bands. They succeed, resulting in Zed, Eliza, and Bonzo turning into "full zombies" and being taken away by the Zombie Patrol.

Most of the cheerleaders, including Addison and Bree, show their sympathy for the zombies at the game. Addison tells the crowd it was Bucky and his followers that led Zed to transform into a full zombie. She then rips off her wig exposing her naturally white hair, which she had hidden due to the residents of Seabrook being against anything different, angering her parents.

Bucky kicks out all of the zombie-supporting cheerleaders following the incident. When the cheerleader competition nears, Addison and Bree find Zed and Bonzo trying to stop Eliza from sabotaging the competition as revenge for Bucky's decision, after Eliza talks with her friends, she realizes that doing so is not the right thing to do. Bucky's team starts to fail because they do not have enough members, so Zoey, Zed's little sister, tries to get in and help him. At first, Zoey is booed by the crowd, but with help from Addison and Zed, the zombies and cheerleaders come together to make a cheer routine during the Cheer competition. Zed and Addison tell each other they love each other in Zombie-Tongue.

The zombies and humans reunite with each other via a block party in Zombietown.