Written by JK Rowling and starring Eddie Redmayne as magizoologist Newt Scamander, the film took more than the rest of the box office top 10 combined.
But its opening weekend haul was lower than for any of the Harry Potter films.
Benedict Cumberbatch’s Doctor Strange fell to second with $17.7million with Trolls third on $17.5m.
Sci-fi movie Arrival, starring Amy Adams, took fourth spot with $11.8million while the comedy Almost Christmas, starring Danny Glover and Gabrielle Union, rounded out the top five with $7million.
Fantastic Beasts has received broadly positive reviews from critics.
Harry Potter creator Rowling has planned scripts for a total of five films in the series.
Top 5 For 2016’s US Weekend Box Office
- Fantastic Beasts and Where to Find Them – $75million
- Doctor Strange – $17.7million
- Trolls – $17.5million
- Arrival – $11.8million
- Almost Christmas – $7million
The first installment is set in New York, and tells the story of a fictional author mentioned in the Potter stories.
Redmayne plays the part of the animal-loving Newt Scamander, who visits New York’s secret community of witches and wizards.
The film is set 70 years before Harry Potter reads his book at his school, Hogwarts.