Avengers: Infinity War broke a global record with $630m (£457m) in ticket sales during its opening weekend.
The figure, estimated by Disney, is despite the fact Marvel Studios' superhero movie is yet to open in China, the world's second-largest film market.
It made $250m (£181.5m) in ticket sales during its opening weekend in the US, narrowly beating Star Wars: The Force Awakens for the highest opening weekend ever.
However, taking inflation into account would mean the Star Wars film still holds the US record, with about $260m (£188.5m) in today's dollars.
Dave Hollis, head of distribution for Disney, said: "To have now the biggest movie of domestic history as one of the Marvel cinematic universe films seems like a fitting tribute to the Marvel Studios team which has had just an astounding, unmatched run in the last decade."
Starring Robert Downey Jr, Benedict Cumberbatch, Scarlett Johansson, Chris Evans, Josh Brolin and many more A-listers, the film had a reported $300m-$400m production budget.
It brings together more than 20 superheroes including Iron Man, Captain America, Spider-Man, Black Widow and Black Panther for an all-out battle with supervillain Thanos.
Plot details have been shrouded in secrecy, but several major characters die or appear to be killed off.
Many film websites and blogs put odds on which characters will not make it with Loki, played by Tom Hiddleston, coming out on top in many.
Last week the directors asked fans not to give away spoilers.
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Anthony and Joseph Russo also encouraged enthusiasts to stay away from social media if they want to enjoy the surprises.
The two-hour and 40-minute film was shot over 18 months, with a sequel due out in May next year.