The feature, which sees the enormous gorilla and reptilian giant set their differences aside and team up to save their species -- and ours -- took in $31.7 million over the weekend in the United States and Canada, according to the figures.
In second place with an estimated $10 million in ticket sales was action film "Monkey Man," which British actor Dev Patel both directs and stars in.
The thriller, set in India, is "ultra-violent, driven by class differences, corruption and personal vengeance," said analyst David A. Gross.
"Foreign stories do not always work in North America; it's working here," he wrote, adding: "it's going to be very profitable."
In third place was "Ghostbusters: Frozen Empire," which took in $9 million.
Co-written by Jason Reitman, whose father Ivan Reitman directed the first "Ghostbusters" in 1984, the film teams a new cadre of ghost catchers with the original cast as they take on a frightening deity trying to launch a new Ice Age.
In fourth place was the horror film "The First Omen," an intrigue between the Catholic Church and the forces of evil. It grossed $8.4 million in North American cinemas.
Relegated to fifth place, "Kung Fu Panda 4," Universal and DreamWorks Animation's martial arts comedy, which earned $7.9 million.