Avengers: Endgame has become the highest-grossing film of all time, outstripping James Cameron's Avatar record for earnings worldwide.

At the weekend the Marvel blockbuster's total earnings ticked over to an estimated $US2.79 billion ($3.96 billion), 13 weeks after its release.

Avatar held on to the record for a decade after its 2009 release, earning a total of $US2.789 billion.

Fanfare for Endgame ramped up early, with the trailer racking up more than 29 million views 11 hours after it was posted on Marvel's official YouTube channel.

The film was forecast to take between $US260 million and $US300 million in its first week of showings in US and Canadian theatres, but moviegoers turned out in such force that the figure jumped to a record $US350 million in sales.

Endgame's running time of 161 minutes did not discourage audiences, with US theatres adding thousands of showings for the film to get it on more screens than any movie before, with some theatres even staying open 72 hours straight.

Joe and Anthony Russo's movie ties together the Avengers storyline as well as the previous 21 releases of the Marvel cinematic universe, which began with 2008's Iron Man.

The movie featured an all-star cast including Robert Downey Jr, Chris Evans, Mark Ruffalo, Brie Larson, Danai Gurira, Tom Holland, Chris Pratt, Scarlett Johansson, Don Cheadle and Australia's Chris Hemsworth.

The title of highest-grossing film comes with a few caveats, however, including the fact that Avatar's earnings are not adjusted for inflation.

Also, in the US, Avengers: Endgame came in second to Star Wars: The Force Awakens, with a difference in earnings of about $US113 million.

While at San Diego Comic-Con on Saturday night Marvel Studios president Kevin Feige gave a shout-out to Avatar director James Cameron for holding the record for so long.

Feige also noted the inflation technicality and said Cameron would probably hold the title again someday.

Hemsworth took to Instagram to thank fans.

"Thank you to all the fans around the world that lifted Avengers: Endgame to historic heights, making it the top grossing film of all time," he wrote.

Portman to star as female Thor

News of Endgame's record-breaking earnings came as it was announced Hemsworth would star alongside Natalie Portman in the fourth instalment of the Thor series.

Thor: Love and Thunder, will be directed by New Zealand's Taika Waititi, who was lauded for his work on Thor: Ragnarok.

Waititi told Comic-Con fans that for the upcoming film he was inspired by the comic source material The Mighty Thor, which introduces female Thor.

"For those of you who know that storyline, it's incredible; it's full of emotion of love and thunder and it introduces for the first time female Thor," he said.

"So, for us there's only one person who could play that role."

Portman played the character Jane in the first two Thor movies.

Thor: Love and Thunder, which will see Tessa Thompson return to the screen, is slated for release in November 2021.

All-star cast rolled out for fans

The Comic-Con presentation also saw an appearance from Angelina Jolie, who will have a starring role in The Eternals, which is expected to be released in November 2020.

Jolie said she was already in training and was going to work 10 times harder than she had on any other action films she had been involved in.

She was joined on stage by fellow cast members Richard Madden, Kumail Nanjiani, Bryan Tyree Henry and Salma Hayek, as well as director Chloe Zhao.

Fans were also treated to a preview of Black Widow, with Johansson showing the audience footage of hand-to-hand combat in Budapest.

The film is being directed by Cate Shortland and features Stranger Things' David Harbour as well as Florence Pugh, O-T Fagbenle and Rachel Weisz.

Johansson said she "battled it out" to have the movie made and said the search for a female director showed "systemic problems" in Hollywood.

"I'm looking forward to exploring [my character] as a fully realised woman in all of her many facets," she said.

Black Widow, which is just a month into production, is due for release in May 2020.

Another big name joining the Marvel ranks is Awkwafina, who will appear in Shang-Chi and the Legend of the Ten Rings, to be released in February 2021.

Unknown actor Simu Liu has been cast to lead Shang-Chi alongside Tony Leung, with Destin Daniel Cretton to direct the film.

A Doctor Strange sequel, Doctor Strange in the Multiverse of Madness, is due to hit cinemas in May 2021, with Benedict Cumberbatch confirmed to be returning to the role.

The film will be directed by Scott Derrickson and will also feature Elizabeth Olsen.

The presentation wrapped up with an announcement that actor Mahershala Ali, from the Oscar-winning film Green Book, would star in the upcoming film Blade.

A release date for Blade has yet to be announced.