The fourth in a long-running science fiction series, the film stars Milla Jovovich as a new age warrior fighting to protect humans from a world led by zombies.
Resident Evil films are based on a video game of the same name from Japan's Capcom. The latest film was directed by Paul Anderson, who also directed the original 2002 feature.
Jumping one spot into second place was Takers. The bank-robbery thriller starring Hayden Christensen, Idris Elba and singers Chris Brown and T.I. earned 5.7 million dollars in its third week of release, bringing its overall take to 47.7 million dollars, said industry tracker Exhibitor Relations.
George Clooney's spy flick The American fell from its top spot to land in third place with earnings of 5.7 million dollars. Mixing violence with a campy tribute to 1970s exploitation movies from directors Robert Rodriguez and Ethan Maniquis, Machete came in fourth with 4.3 million dollars from Friday to Sunday, or 20.9 million since its release.
Holding steady at number five was new release Going the Distance, a romantic comedy starring Drew Barrymore and Justin Long about a couple living on opposite US coasts who try to make their relationship work. It earned 3.8 million dollars in its second weekend.
The Other Guys, the latest Will Ferrell slapstick comedy, climbed up one spot to sixth place, taking in 3.3 million dollars for its story about two mismatched police officers paired on a high-profile crime investigation.
Seventh place went to the gruesome documentary-style horror movie The Last Exorcism, which fell from its fourth spot last weekend, taking 3.3 million dollars, or 38 million since its release.
The mockumentary, directed by Daniel Stamm and co-produced by Eli Roth, a director known for his bloody thrillers, follows a disillusioned minister supposedly filming his last exorcism for a documentary.
Falling to eighth place was The Expendables, Sylvester Stallone's film about a group of weathered mercenaries out to topple a South American dictator, which earned 3.2 million dollars in its fifth week in theaters.
Eat, Pray, Love, Ryan Murphy's adaptation of Elizabeth Gilbert's novel about a divorcee's jaunt to Italy, Indonesia and India, starring Julia Roberts, took ninth position with 2.9 million dollars.
