The feature by British director Alex Garland stars Kirsten Dunst as a journalist travelling through a broken country, in which a three-term president battles secessionist forces from California and Texas.
The movie -- which has highlighted fears about the divided state of the nation ahead of November's presidential election -- raked in $25.7 million in the US and Canada, Exhibitor Relations reported Sunday.
That is more than twice the average for a dystopian thriller on its opening weekend, said analyst David A. Gross.
Such movies "are generally set in futuristic worlds that look very different from contemporary life, Gross wrote.
"Civil War is doing the opposite: It looks like right now. The film is bending the genre into something contemporary and relatable. The story is not directly partisan, but it's provoking partisan feelings," he added.
"It's a fine balance to strike. Audiences are emotionally engaged, and that's impressive for a thriller."
The film knocked "Godzilla x Kong" into second place.
That feature, which sees the enormous gorilla and reptilian giant team up to save their species -- and ours -- took in an estimated $15.4 million.
Third place went to "Ghostbusters: The Ice Menace," with $5.8 million. In the latest installment of the popular franchise, the ghost hunters face the threat of a new ice age.
"Kung Fu Panda 4," Universal and DreamWorks Animation's martial arts comedy, climbed one spot back to fourth place with its $5.5 million.
As for "Dune: Part II", which took in $4.3 million, it still hasn't bogged down after seven weeks in theaters, and also climbed one place since the previous weekend.
Denis Villeneuve's science-fiction film has grossed $272 million since its release in early March.
Here's the rest of the top 10:
"Monkey Man" ($4.1 million)
"The First Omen" ($3.8 million)
"The Long Game" ($1.4 million)
"Shrek 2" (special 20th anniversary re-release) ($1.3 million)
"SUGA Agust D TOUR 'D-DAY' THE MOVIE" ($991,000)
