The Narrator, Columbus (going by the name of where he’s from) (Jesse Eisenberg) starts by telling us about how the plague began. Mad cow disease mutated and created Patient Zero. Patient Zero spread the plague until most of the world was wiped out. Columbus survived because he was a bit of a shut in. His neurosis peaked at college and so, when the plague hit, he stayed indoors mooching off of pizza, Mountain Dew code red and playing World of Warcraft.
He didn’t plan to leave his dorm, but the night the epidemic began, Columbus was sitting around when his hot neighbor “406” started knocking on his door. He opened the door and 406 (Amber Heard) tells him about the “crazy psycho” who tried to take a bite out of her. Columbus gives her some Mountain Dew and lets her rest on his couch. They fall asleep together. When Columbus wakes up, 406 is a zombie and attacks him. She chases him around the apartment until he makes it to the bathroom. Columbus breaks her leg and then smacks her in the face with a toilet lid. She gets up and tries to attack him again, so Columbus puts her down with a second smack.
In the present, Columbus survives following a set of rules. At a gas station, he refuels his car and needs to use the bathroom but remembers that the zombies are aware of where people are off guard. He explains that the one thing which scares him worse than zombies are clowns and imagines a clown looking at him as he’s taking a dump. As he nears the bathroom, a zombie bursts out and attacks while another zombie circles from behind. Columbus runs around in circles until he successfully gets into his car, which he left unlocked. He starts to drive away when a zombie appears in his back seat. Columbus crashes the car and after sending the zombie through the windshield shoots it in the head. Columbus collapses against his car and craps himself.
The next morning, Columbus is travelling down an abandoned highway when a car comes zooming down the highway. The driver sees Columbus even as he tries to hide and stops his car. The driver, from Tallahassee (Woody Harrelson), steps out and the two point their guns at one another. Columbus asks for a ride and Tallahassee accepts. They don’t use their real names since it would only foster attachment. Tallahassee agrees to take Columbus as far east as the next town but notes that their personalities clash.
Tallahassee tells Columbus that he lost the only thing that meant anything to him. His “little pup” was the only thing that mattered to him. He’d wash it, walk it and make it breakfast every morning. The zombies took care of him, so Tallahassee doesn’t have anything left except killing zombies.
On the way to the next town, they see a Hostess truck crashed off the side of the road. Tallahassee is in search of one of the world’s last Twinkie, so he climbs down but finds it’s full of Snow Balls. This pisses Tallahassee off and forces them to continue on their journey.
Tallahassee pulls over to a grocery store and goes through weapons in the back of his car he takes a metal bat, banjo and some hedge clippers and goes to town. He kills the three zombies in the store easily. Columbus is impressed, but their congratulations are short lived when they see Wichita (Emma Stone). Wichita tells them to come quick since her little sister, Little Rock (Abigail Breslin), has been bitten.
Tallahassee agrees to put Wichita down even though he is clearly uncomfortable with the situation. Wichita asks if she can be the one to do it, so Tallahassee hands her the gun. Wichita and Little Rock then hold the two hostage and steal their car, stranding them in the supermarket without any weapons.
Wichita and Little Rock were con girls before the plague, so they apply their skills in Zombieland to their advantage.
Tallahassee is pissed at this turn of events and the two carry their stuff all the way to a nearby set of suburbs. Tallahassee loses his temper and bashes the crap out of a minivan on the side of the road. He then notices a Hummer and the duo find a fully stocked arsenal in the back of the hummer. The pair head west to catch up with Wichita and Little Rock. Columbus is clearly in love with Wichita, and Tallahassee points out that “it’s ok to want to fuck her. Hell she fucked both of us twice already.”
They see their old car abandoned on the side of the road. Tallahassee goes to the car with the intention of shooting them, but the car is abandoned. He returns to Columbus and once he buckles up, realizes that Little Rock is in the back seat with a gun pointed at them. They group start driving around and Wichita tells them about how they are going to an old amusement park near Hollywood which will be zombie free. She wants to give her little sister something to believe in. Columbus asks if they heard about Columbus, Ohio and Wichita tells him it burned to the ground and that everyone is dead. Columbus is in shock and Tallahassee hits Wichita and points out what she did.
The group stops at an out of the way Native Indian store. They look around and then trash the store in order to entertain themselves. Columbus puts on a bit of cologne and Tallahassee makes fun of him for putting on perfume. When the group leaves, Wichita points out that Columbus smells like perfume.
That night, while Wichita drives and Tallahassee and Little Rock sleep, Wichita apologizes for her insensitivity. The two bond and Columbus decides to stay because Wichita is someone he has always wanted to be with.
The next morning, Tallahassee drives the group into Hollywood and they tour the celebrity mansions. Tallahassee drives them to the best mansion of them all: Bill Murray’s. Little Rock has never heard of Bill Murray, so Columbus takes her into Bill Murray’s home theater and the two watch Ghostbusters while talking about Wichita. Wichita and Tallahassee explore the house and encounter Bill Murray, dressed as a zombie. He uses camouflage to travel around among the zombies and easily gets around Hollywood on the theory that Zombies don’t mess with other Zombies. Tallahassee sings Murray praises and then Murray decides to play a joke on Columbus. He sneaks up on them in the theater and Columbus ends up shooting Murray and killing him. The group gives him a salute and then tosses his body off the roof.
That night the group fools around in the mansion. While playing monopoly, Tallahassee talks about his “little pup” again and Columbus realizes that it wasn’t a dog. Tallahassee had a son and once he lost him, he became a vengeful man whose only pleasure comes from killing the undead. Columbus feels for his friend and ends up alone with Wichita. Wichita and Columbus get drunk together and dance. Wichita tells Columbus that she would totally “hit that” when she thinks about whether or not they should sleep together. They are about to kiss when Tallahassee comes in asking for help. Wichita tells Columbus that she and her sister will do anything to survive. They drive away the next morning, leaving Columbus and Tallahassee behind.
The girls arrive at the theme park that night and turn on all the equipment. This draws all the zombies in the area to the park and causes a lot of problems for the girls. They take refuge on the Space Drop and short out the mechanics so that they would be safe high above the zombies. As zombies start climbing up to get them, Tallahassee and Columbus arrives. Tallahassee lures the zombies away from the girls and sends Columbus to rescue them. Columbus is chased by zombies through a haunted house but escapes. Tallahassee goes around the theme park killing zombies while using the rides. The girls run out of bullets on the Space Drop as two zombies climb up to get them.
With only two pistols and 4 extra clips, Tallahassee is forced to retreat to a carnie prize kiosk for his last stand. Columbus is about to reach the girls when he runs into a giant zombie clown. He notes the irony in the situation and proceeds to beat it to death and rescue the girls. In the end, all the zombies in the park are dead and the group is safely reunited.
Tallahassee and Columbus go to a Fried Twinkie shack in the park and look for Twinkies. Tallahassee starts to lose it when they hear a noise in the backroom. Columbus shoots the door but it turns out there was only a rat inside. The box of Twinkies was destroyed when Columbus shot the door. Tallahassee is pissed and about to hurt Columbus when they hear their car pulling away. Little Rock tosses a Twinkie she found when they arrived at the park to Tallahassee and Tallahassee eats the delicious cake and truly enjoys it. The group drives away together, noting that they are now like a little family.
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