The animated sequel about toys that come to life leaped to the No. 1 spot with a $109 million opening weekend, according to studio estimates Sunday.
"Toy Story 3" became the third animated film to top $100 million in the first weekend, joining "Shrek the Third" at $121.6 million and "Shrek 2" at $108 million.
It was by far the best debut for a film from Disney's Pixar Animation, topping "The Incredibles" at $70.5 million.
Reuniting voice stars Tom Hanks and Tim Allen, the movie has Woody the cowboy, Buzz Lightyear and their toy pals facing their mortality, worried they will end up on the scrap heap now that their kid has grown up.
"Whether you're a kid or a parent, you always come to a fork in the road where you make the decision of what to do about your toys. Therein lies the appeal of the movie," said Chuck Viane, head of distribution for Disney.
That, and the fact that Woody, Buzz and the gang have become like family to "Toy Story" fans, he said.
"Somehow these characters have worked their way in. When you go there, you can see the audience is vested in the movie from the start. It doesn't take any time to warm up. The minute it hits the screen, they're in," Viane said.
"Toy Story 3" took over the No. 1 spot from Sony's "The Karate Kid," which pulled in $29 million to raise its 10-day total to $106.3 million.
The weekend's other new wide release, the Warner Bros. action tale "Jonah Hex," bombed with just $5.1 million. Adapted from the comic book series, "Jonah Hex" stars Josh Brolin as a disfigured 19th century bounty hunter tracking a villain who aims to unleash a doomsday weapon.
"Toy Story 3" took in an additional $44.8 million overseas, giving it a worldwide total of $153.8 million. The movie has opened in such countries as Mexico, Argentina and China but will not debut in most major foreign markets until July and August.
The film also maintains the perfect track record of Pixar, whose 11 films all have opened at No. 1, starting with the original "Toy Story" in 1995 and continuing with such hits as "Finding Nemo," ''Ratatouille," ''WALL-E" and last year's "Up."
"Disney-Pixar is the best box-office insurance policy you can have," said Paul Dergarabedian, box-office analyst for Hollywood.com. "It's a brand that just resonates with audiences. If they go to a Pixar movie, they know they're going to be entertained. They're going to have a great time and also get a message. There's always a positive lesson you walk away with."
The film gave a nice boost to Hollywood, whose overall receipts had lagged in May. Domestic revenues totaled $198 million, up 31 percent from the same weekend last year, when "The Proposal" led with $33.6 million.
"Toy Story 3" continued Hollywood's streak of 3-D hits. The 3-D version of the film accounted for 60 percent of revenues, though it played on more 2-D than 3-D screens, according to Disney.
Tickets for 3-D movies typically cost a few dollars more than 2-D versions.
"Toy Story 3" took in $8.4 million in 3-D showings at huge-screen IMAX theaters. That beat the IMAX record for an animated film previously held by "Monsters vs. Aliens" with $5.1 million.
In limited release, Fox Searchlight's comedy "Cyrus" debuted strongly with $180,289 in four theaters, averaging $45,072 a cinema, compared to $27,061 in 4,028 locations for "Toy Story 3."
"Cyrus" stars John C. Reilly, Marisa Tomei and Jonah Hill in the tale of a man whose new romance is jeopardized by his girlfriend's grown son, who wants his mom to himself. The film gradually expands to nationwide release through mid-July.
Estimated ticket sales for Friday through Sunday at U.S. and Canadian theaters, according to Hollywood.com. Final figures will be released Monday.
1. "Toy Story 3," $109 million.
2. "The Karate Kid," $29 million.
3. "The A-Team," $13.8 million.
4. "Get Him to the Greek," $6.1 million.
5. "Shrek Forever After," $5.5 million.
6. "Prince of Persia: The Sands of Time," $5.3 million.
7. "Killers," $5.1 million.
8. "Jonah Hex," $5.09 million.
9. "Iron Man 2," $2.7 million.
10. "Marmaduke," $2.65 million.