The romantic comedy, which stars Natalie Portman and Ashton Kutcher, toppled last week's number one, taking $20.3 million.
Seth Rogen's superhero flick The Green Hornet falls to second place taking $18.1 million, followed by Vince Vaughn's comedy The Dilemma which took $9.7 million.
Colin Firth's critically acclaimed historical drama The King's Speech remains in fourth with $9.1 million, followed by the Coen Brothers' True Grit, which rounds out the top five with takings of $8 million.
Next week sees the release of a new horror in the form of Antony Hopkins's latest film The Rite, as well as the Jason Statham-led action remake of The Mechanic.
The US box office top ten in full:
1. (-) No Strings Attached - $20,300,000
2. (1) The Green Hornet - $18,100,000
3. (2) The Dilemma - $9,720,000
4. (4) The King's Speech - $9,100,000
5. (3) True Grit - $8,000,000
6. (5) Black Swan - $6,200,000
7. (9) The Fighter - $4,515,000
8. (6) Little Fockers - $4,390,000
9. (8) Yogi Bear - $4,060,000
10. (7) Tron: Legacy - $3,700,000