Finding Dory has taken $136.2m (£93.3m) on its opening weekend - making it the most successful launch for an animated film in US box office history.
The sequel to Finding Nemo has unseated Shrek the Third - which took $121.6m (£83.1m) on its release in 2007.
It is also the second most successful opening weekend of 2016, behind Marvel's Captain America: Civil War.
Ellen DeGeneres voices the lead character in Finding Dory, which is released in the UK on 29 July. She also voiced Dory in Finding Nemo, which came out in 2003.
Paul Dergarabedian, comScore's senior media analyst, said: "The thought was 'could this be the movie to eclipse Toy Story 3's opening, not, 'could it become the biggest animated opening of all time?'.
"That's the power of the Pixar brand."
Variety added it had succeeded where many sequels had failed, saying one of the reasons was its appeal to female cinema-goers:
It said: "Dory represent a wider range of female experiences and boast character traits beyond simply waiting around for their prince. They are archers, cops, teenage girls, even forgetful fish."
Toy Story 3 was the biggest Pixar opening until now with $110.3m (£75.4m).
Finding Dory's closest competitor over the weekend, Central Intelligence starring Dwayne Johnson and Kevin Hart, landed in second place after taking $34.5m (£23.6m) on its opening weekend.
"It's a real home run," said Jeff Goldstein, Warner Bros' executive vice president of domestic distribution.
"These two comedians are just stars. They connect with their audience and each other in such a strong way. You just laugh when you watch them."
The two films pushed last week's number one, The Conjuring 2, down to number three.
Now You See Me 2 and Warcraft rounded off the top five. ?BBC