The 3-hour film starring Robert Downey Jr., Chris Hemsworth and Scarlett Johansson is the final chapter in a story told across 22 Marvel films. It picks up after "Infinity War," when many of Marvel's big-screen superheroes appeared to turn to dust.
Marvel superhero spectacle "Avengers: Endgame" hauled in a record $60 million at U.S. and Canadian box offices on Thursday night, and distributor Walt Disney Co "cautiously" predicted an unprecedented $300 million weekend debut.
That would smash the current opening-weekend domestic record of $258 million, set a year ago by predecessor "Avengers: Infinity War."
"As we are looking at levels of presales and grosses not seen before, we are cautiously projecting a three-day in the $300 (million) range," Disney said in an e-mail on Friday afternoon.
In "Endgame," survivors including Iron Man, the Hulk and Black Widow plot to kill the supervillain Thanos and undo his damage.
Thursday evening's domestic sales topped the previous opening night record of $57 million set in 2015 by "Star Wars: The Force Awakens."
"Endgame" began rolling out in international markets on Wednesday and has achieved records in China and several other countries. As of Friday morning, global ticket sales reached $305 million, Disney said.