The comic book superhero blockbuster made $55.1 million over the weekend in North America, said box office tracker Exhibitor Relations.
The film has become the highest-grossing movie in Walt Disney Studios history with global earnings exceeding $1 billion, according to industry website IMDb.
"The Avengers" -- which include Iron Man, the Incredible Hulk, Captain America and Thor -- was directed by cult favorite Joss Whedon in collaboration with Marvel Comics and made for an estimated $220 million.
The movie's success will help mitigate Disney's $200 million loss on the sci-fi fantasy film "John Carter" in March, which prompted the departure of Walt Disney Studios boss Rich Ross.
"The Avengers" pounded new release "Battleship," which earned the number two spot and about $25.4 million in its debut weekend.
Trailing "Battleship" was comedian Sacha Baron Cohen's wacky "The Dictator," which scored a third place finish and $17.4 million in its premier weekend.
Next was Tim Burton's new Johnny Depp vampire flick "Dark Shadows," in fourth place with $12.7 million.
Newcomer "What to Expect When You're Expecting" opened in fifth place with $10.5 million, followed by "The Best Exotic Marigold Hotel," a comedic drama about British retirees in India, that netted $3.25 million.
In the seventh spot was smash action hit "The Hunger Games." The movie, starring Jennifer Lawrence, earned $3.0 million and has raked in more than $387 million in North America since its opening.
Romantic comedy "Think Like A Man" dropped to eighth place earning $2.7 million, followed by tearjerker "The Lucky One," an adaptation of a Nicholas Sparks book starring Zac Efron of "High School Musical" fame as a US soldier back from Iraq. The movie made $1.8 million.
"The Pirates! Band of Misfits," a children's animation film from the studio that produced the "Wallace and Gromit" series was in 10th place earning $1.45 million.