The record-breaking four-day weekend generated estimated receipts of $316 million.
"Over $300 million for Memorial Day weekend has never happened before," said box-office analyst Paul Dergarabedian of Hollywood.com. "This proves that when you have a great selection of films, audiences will line up at movie theatres in record numbers."
The sixth installment of the "Fast & Furious" franchise debuted at No. 1 with $120 million, making it the biggest opening weekend for a Universal Pictures release, according to Hollywood.com.
Starring Vin Diesel and Paul Walker, the muscle-car action romp took in an additional $158 million internationally.
Fans turned out because filmmakers upped the ante, said Nikki Rocco, Universal's head of distribution.
"The creative team, the filmmakers and the studio put their heart and soul into making it bigger and better," she said. "When you have this many films in the franchise ... you have to take it in a new direction."
The street racers battle both a tank and a plane in the film.
"It is the very definition of the summer popcorn movie," Dergarabedian said. "You suspend disbelief, buckle up and go along for that ride."
"The Hangover Part III," starring Zach Galifianakis, Bradley Cooper and Ed Helms, opened in second place. The final chapter in the Warner Bros. raunchy comedy trilogy collected $51.2 million.
Paramount Pictures' "Star Trek: Into Darkness," which opened last week, added $47 million to its domestic ticket sales, landing at No. 3.
Fox' animated "Epic," the only non-sequel among the weekend's five top-grossing films, opened in the fourth spot with $42.6 million.
"We did see a hole in the release schedule that said this is the perfect time to launch an animated film," said Fox president of domestic distribution Chris Aronson. "It can be challenging to launch an original-content movie in such a competitive weekend, but this is a very special movie: A family movie as well as an all-audience movie."
Now in its fourth week of release, "Iron Man 3" — which had the biggest opening so far this year — hung onto fifth place with $24.4 million.
The record-breaking weekend take bodes well for the summer movie season, Dergarabedian said: "This Memorial weekend is exactly what the industry needed and this momentum will carry forward."
Estimated ticket sales for Friday through Monday at U.S. and Canadian theatres, according to Hollywood.com. Where available, latest international numbers are also included. Final domestic figures will be released Tuesday.
1. "Fast & Furious 6," $120 million ($158 million international).
2. "The Hangover Part III," $51.2 million ($19.2 million international).
3. "Star Trek: Into Darkness," $47 million ($13.1 million international).
4. "Epic," $42.6 million ($23.1 million international).
5. "Iron Man 3," $24.4 million ($17.4 million international).
6. "The Great Gatsby," $17 million ($24.4 million international).
7. "Mud," $2.5 million ($400,000 international).
8. "The Croods," $1.6 million ($5.8 million international).
9. "42," $1.6 million.
10. "Oblivion," $1.1 million ($2.3 million international).
Estimated weekend ticket sales at international theatres (excluding the U.S. and Canada) through Sunday for films distributed overseas by Hollywood studios, according to Rentrak:
1. "Fast & Furious 6," $158 million.
2. "The Great Gatsby," $24.4 million.
3. "Epic," $23.1 million.
4. "The Hangover Part III," $19.2 million.
5. "Iron Man 3," $17.4 million.
6. "Star Trek: Into Darkness," $13.1 million.
7. "The Croods," $5.8 million.
8. "Oblivion," $2.3 million.
9. "Evil Dead," $2.2 million.
10. "Only God Forgives," $1.5 million.
Follow AP Entertainment Writer Sandy Cohen on Twitter at www.twitter.com/APSandy .
Universal and Focus are owned by NBC Universal, a unit of Comcast Corp.; Sony, Columbia, Sony Screen Gems and Sony Pictures Classics are units of Sony Corp.; Paramount is owned by Viacom Inc.; Disney, Pixar and Marvel are owned by The Walt Disney Co.; Miramax is owned by Filmyard Holdings LLC; 20th Century Fox and Fox Searchlight are owned by News Corp.; Warner Bros. and New Line are units of Time Warner Inc.; MGM is owned by a group of former creditors including Highland Capital, Anchorage Advisors and Carl Icahn; Lionsgate is owned by Lions Gate Entertainment Corp.; IFC is owned by AMC Networks Inc.; Rogue is owned by Relativity Media LLC.