Directed by cult favorite Joss Whedon, the Walt Disney high-thrills action adventure made in collaboration with Marvel Comics looked set to become the highest grossing US debut of all time.
Heroes Captain America, The Incredible Hulk, Iron Man and Thor are brought together as an international peacekeeping agency of superheroes battling to save Earth from Thor's evil brother Loki and his army of aliens.
The film's all-star cast includes Gwyneth Paltrow, Samuel L. Jackson (Nick Fury), Scarlett Johansson (Black Widow), Jeremy Renner (Hawkeye), Robert Downey Jr (Iron Man), Chris Evans (Captain America), Mark Ruffalo (Hulk), and Chris Hemsworth (Thor), most of the latter reprising roles from earlier stand-alone movies.
Walt Disney said the film, which was released first abroad before hitting US shores, had already raked in some $641.8 million and reports said it was on target to join the elite club of the world's few billion dollar movies.
Takings from its first three days meant "The Avengers" had outstripped expectations and surpassed the $168.2 million taken on its opening weekend by "Harry Potter and the Deathly Hallows - Part 2" -- the eighth and final film in the hugely-popular series.
"Such strong grosses signaled that this was not just a fan movie -- not just a guy movie -- but a movie for everyone," Dave Hollis, Disney's executive vice president for distribution told the Los Angeles Times.
It will be a huge relief to Disney, which spent some $220 million to produce the film, after its very public box office flop "John Carter" earlier this year which caused a $200 million write-down -- one of the biggest losses of all time, according to the LA Times.
"The Avengers" kicked romantic comedy "Think Like A Man" into second place earning $8 million, according to Exhibitor Relations. That brings its three-week total to $73.0 million, the box office tracker said.
Smash action hit "The Hunger Games" remained in third place in its seventh week on the big screen. The movie, starring Jennifer Lawrence, earned $5.7 million and has raked in more than $380 million since its opening.
Legions of fans have flocked to see the film, based on a book by Suzanne Collins, in which a teenage girl played by Lawrence fights to win a deadly television reality show featuring children in a post-apocalyptic world.
Tearjerker drama "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, held onto fourth place. The movie made $5.5 million in its third weekend.
In fifth place was "The Pirates! Band of Misfits," a children's animation film from the studio that produced the "Wallace and Gromit" series earning $5.4 million on its second weekend and moving down from second place.
"The Five-Year Engagement," starring Emily Blunt and Jason Segel, dropped to sixth place, with $5 million.
"The Raven" starring John Cusack as 19th century American author Edgar Allan Poe, which has had mediocre reviews, lingered in seventh place with $2.5 million.
And the Jason Statham action flick "Safe" dropped down from sixth to eighth place with $2.4 million.
"Chimpanzee," a true-life, child-friendly adventure about a special chimp in the jungles of Ivory Coast also from the Walt Disney stable, sank to ninth, with $2.3 million.
The Farrelly brothers' comedy "The Three Stooges" rounded out the week's top 10, taking bottom place in its fourth week. The tribute to the legendary US comedy trio brought in $1.8 million.