The fifth installment of the zombie thriller series, based on the popular video game franchise and starring Milla Jovovich, blasted its way to number one, grossing $21.1 million (£13.2 million).
Finding Nemo 3D, a reformatted version of the 2003 animated movie, swam its way into second place with $17.5 million (£10.9 million) in takings.
Last week's (ends09Sep12) biggest hit, creepy horror The Possession, slipped to number three with $6 million (£3.75 million).
Meanwhile, director Paul Thomas Anderson's new film The Master, which is loosely based on the story of late author and Church of Scientology founder L. Ron Hubbard, has proved to be a big hit, becoming the strongest limited release debut in U.S. box office history.
The drama, which stars Philip Seymour Hoffman as the leader of a controversial faith dubbed The Cause and Joaquin Phoenix as his conflicted protege, opened with an impressive $729,745 (£456,091) from just five locations in New York and Los Angeles, garnering an average of $145,949 (£91,218) per screen.