The Universal Pictures laugher starring the "Saturday Night Live" duo crawled past Warner Bros.' "Harold & Kumar Escape from Guantanamo Bay," the goofy stoner flick that opened at No. 2 with $14.6 million.
With a third comedy, Universal's "Forgetting Sarah Marshall," holding its own at No. 4 with $11 million, audiences looked to be flocking to theaters to get giddy.
"Comedy is definitely king right now," said Paul Dergarabedian, president of tracking firm Media By Numbers LLC. "Audiences are definitely showing an interest in going to the movies and having a good time and having a laugh."
Lionsgate's kung fu movie "The Forbidden Kingdom" starring Jackie Chan and Jet Li fell two notches to No. 3 with $11.2 million.
Critics had questioned Universal's decision to release "Baby Mama" so closely on the heels of "Forgetting Sarah Marshall," thinking it would cannibalize the comedy-seeking public.
"I think there's something to be said about the Hollywood myth that you can't open a comedy against a comedy," said Nikki Rocco, Universal's president of distribution. "We just proved that to be wrong."
The success of the first "Harold & Kumar" sequel also showed audiences are not too sensitive to laugh at post-Sept. 11 topics like terrorism. The movie premise begins with the pair getting in trouble trying to sneak a bong on a flight to Amsterdam, then escaping the U.S.-run prison for alleged terrorists in Cuba.
"I don't think anybody takes this too seriously," said Dan Fellman, Warner Bros.' president of theatrical distribution.
The sequel cost just $12 million to make and is already close to beating the entire theatrical take of $18.2 million for the first "Harold & Kumar" movie.
"Hopefully we'll do somewhere in the $40 million range," Fellman said.
It was the second straight weekend that has shown better revenue than the previous year, following four "down" weekends, Dergarabedian said. The weekend gross for the films measured was up 17 percent at $91 million.
For the year to date, however, box office revenue is down 2.7 percent at $2.59 billion, with attendance off 5.4 percent.
Still, the recent upswing is "the perfect lead-in to the start of the summer movie season" which gets under way next weekend with the debut of "Iron Man," Dergarabedian said.
Estimated ticket sales for Friday through Sunday at U.S. and Canadian theaters, according to Media By Numbers LLC. Final figures will be released Monday.
1. "Baby Mama," $18.3 million.
2. "Harold & Kumar Escape from Guantanamo Bay," $14.6 million.
3. "The Forbidden Kingdom," $11.2 million.
4. "Forgetting Sarah Marshall," $11 million.
5. "Nim's Island," $4.5 million.
6. "Prom Night," $4.4 million.
7. "21," $4 million.
8. "88 Minutes," $3.6 million.
9. "Dr. Seuss' Horton Hears a Who!", $2.4 million.
10. "Deception," $2.2 million.