The Disney-Pixar animated sequel opened with a solid $68 million in returns, a higher gross than the original "Cars" movie in 2006.
It also marks 12 box office wins in a row for Pixar since the company's first feature film, "Toy Story," in 1995.
Opening in second place was the Cameron Diaz comedy "Bad Teacher" with a higher-than-expected $31 million.
The top 10 movies of the weekend were:
1. "Cars 2," $68 million ($42.9 million international).
2. "Bad Teacher," $31 million ($12.9 million international).
3. "Green Lantern," $18.4 million.
4. "Super 8," $12.1 million ($10.5 million international).
5. "Mr. Popper's Penguins," $10.3 million.
6. "X-Men: First Class," $6.6 million.
7. "The Hangover Part II," $5.9 million.
8. "Bridesmaids," $5.4 million ($11.5 million international).
9. "Pirates of the Caribbean: On Stranger Tides," $4.7 million
($13.5 million international).
10. "Midnight in Paris," $4.5 million.
The Associated Press contributed to this report.
