The film stars Harrelson alongside Jesse Eisenberg
Comedy Zombieland has topped the North American box office, scoring Woody Harrelson the biggest film opening of his career.
The movie, which features the star as a killer fighting an epidemic of the undead, took $25m (£15.7m) in its opening weekend.
Harrelson's previous best opening was 1993's Indecent Proposal which took $18m (£11.3m)
Family animation Cloudy With a Chance of Meatballs slipped to number two.
US BOX OFFICE TOP FIVE
1 Zombieland -$25m
2 Cloudy With A Chance of Meatballs - $24.6m
3 Toy Story & Toy Story 2 3D - $12.5m
4 The Invention of Lying -$7.4m
5 The Surrogates - $7.3m
The top 10 featured four other new releases in a weekend where sales were generally down.
A 3D double-feature re-issue of Pixar's Toy Story and Toy Story 2 opened at three with $12.5m (£7.4m), ahead of the release of Toy Story 3 in 3D next June.
Ricky Gervais comedy The Invention of Lying, which takes place in an alternate reality where everyone tells the truth, debuted at number four.
Michael Moore's Capitalism: A Love Story took $4.85m (£3m) despite only showing in 962 cinemas.
It tied in sixth place with Drew Barrymore's directorial feature debut Whip It starring Ellen Page as a teenager who attempts to escape small town life by taking up roller derby, a contact sport of speed roller skating.