Cupid struck on St. Valentine's Day weekend (12-14Feb10) as millions flocked to watch the romantic comedy, which stars Julia Roberts, Jessica Alba, Jennifer Garner, Anne Hathaway, Ashton Kutcher and Bradley Cooper, among others.
The box office figures are expected to swell by the end of Monday (15Feb10) as U.S. film fans take advantage of the Presidents Day holiday and three-day weekend.
Valentine's Day has already smashed the previous Presidents Day weekend record of $52 million (£32.5 million) set by Ghost Rider in 2007.
Meanwhile, Pierce Brosnan's Percy Jackson and the Olympians: The Lightning Thief enters at two with $31.1 million (£19.44 million), while Benicio Del Toro's The Wolfman grossed $30.6 million (£19.23 million) in its opening weekend to claim third place.
James Cameron's sci-fi blockbuster Avatar remains strong at four and last week's (05-07Feb10) number one movie, Dear John, rounds out the top five in fifth position.