The film also dominated the international arena and features the regular voice cast of Dan Castellenata, Julie Kavner, Nancy Cartwright and Hank Azaria.
The strong debut played a major part in raising weekend box office 45% higher than the comparable weekend in 2006, as the top 12 titles combined for $168.6m.
Last weekend's top two, Universal's comedy I Now Pronounce You Chuck And Larry and Warner Bros' Harry Potter And The Order Of The Phoenix, each shunted down a place on $19.1m for $71.6m and $17.1m for $241.8m respectively.
Warner Bros' romantic comedy No Reservations starring Catherine Zeta-Jones and Aaron Eckhart opened in fifth place on $11.8m.
TriStar released Lindsay Lohan thriller with no screenings for critics and its feeble ninth position opening with $3.4m only adds to the predicemant of its troubled star, not to mention the poisonous reviews which emerged on Friday and Saturday.
Dimension's comedy Who's Your Caddy opened in 10th place through MGM on $2.9m.
In its second weekend New Line's musical adaptation Hairspray continued to perform well, dropping one place to fourth on $15.6m for $59.3m.
DreamWorks/Paramount's Transformers in sixth place is bearing down on $300m as $11.5m raised the tally to $284.6m after four. Disney's Ratatouille ranked seventh and added $7.2m for $179.7m in its fifth weekend, while Fox's Live Free Or Die Hard ranks eighth and has amassed $125.1m after the same amount of time.
Meanwhile The Weinstein Company's Michael Moore documentary Sicko, released by Lionsgate, added $1.2m for $21.5m and is expected to become the fourth biggest documentary release in history on Monday when it passes the $21.554 final gross of Moore's Bowling For Columbine.
Next weekend's wide releases are: Universal's thriller The Bourne Ultimatum starring Matt Damon; Disney's family film Underdog; Lionsgate's teen comedy Bratz; and Paramount's comedy Hot Rod with Andy Samberg, Ian McShane and Sissy Spacek.
Estimated Top 10 North America Jul 27-29, 2007
Film (Dist)/Int'l dist/Est wkd gross/Est total to date
1 (-) The Simpsons Movie (Fox) Fox International $71.9m -
2 (1) I Now Pronounce You Chuck And Larry (Universal) UPI $19.1m $71.6m
3 (2) Harry Potter And The Order Of The Phoenix (Warner Bros) WBPI
4 (3) Hairspray (New Line) NLI $15.6m $59.3m
5 (-) No Reservations (Warner Bros/Village Roadshow) WBPI $11.8m -
6 (4) Transformers (Paramount) PPI $11.5m $284.6m
7 (5) Ratatouille (Buena Vista) BVI $7.2m $179.7m
8 (6) Live Free Or Die Hard (Fox) Fox Int'l $5.4m $125.1m
9 (-) I Know Who Killed Me (TriStar) Summit $3.4m -
10 (-) Who's Your Caddy (MGM/Dimension) $$2.9m -