- Woody Harrelson as Tallahassee, Columbus's trusted partner. He despises zombies, and enjoys killing and torturing them.
- Jesse Eisenberg as Columbus, a young man who lived by himself in a beat-up apartment before becoming one of the few survivors of the zombie apocalypse. He lives by a strict set of rules to stay alive. The character is also the narrator of the film.
- Emma Stone as Wichita/Krista, Little Rock's older sister and Columbus's love interest. She is one of the few survivors of the zombie apocalypse, distrustful of strangers, and overly protective of her little sister.
- Abigail Breslin as Little Rock, Wichita's 12-year-old sister. She is sweet, but not that innocent and has had to grow up very quickly because of the apocalypse.
- Bill Murray as a fictionalized version of himself, still living in his Los Angeles home and regularly disguising himself as a zombie to travel around the area.[20] The cameo role was originally written for Patrick Swayze, but he was battling pancreatic cancer at the time and was too sick to make it to set.[21][22] Swayze died in September 2009.[23] Other casting considerations included Sylvester Stallone, Dwayne Johnson, Matthew McConaughey, Jean-Claude Van Damme, Joe Pesci, Mark Hamill, Kevin Bacon, and Dustin Hoffman.[24]
- Amber Heard as 406, Columbus's ill-fated neighbor who becomes the first zombie he kills.[25]
Character names
The main characters do not use each other's real names, but identify themselves using place names (Columbus, Tallahassee, Wichita, and Little Rock) that relate to them. This includes Columbus's neighbor, named 406 after her room, and his fictional sexual conquest Beverly Hills, as well as Sister Cynthia Knickerbocker, whom Columbus identifies as a "Zombie Kill of the Week" winner, and whose surname is actually an obsolete term for a citizen or inhabitant of New York City.[26] The one exception is Murray playing himself. At the end of the film, Wichita tells Columbus that her real name is Krista.[27]
