In an unprecedented takeover of the box office by women, Warner Bros. and New Line’s “Sex and the City” grossed an estimated $55.7 million — racking up the best opening ever for an R-rated comedy and beating holdover “Indiana Jones and the Kingdom of the Crystal Skull” for the weekend crown.

The film’s unexpected boffo performance mystified Hollywood and shattered the decades-old thinking that females — particularly older ones –can’t fuel the sort of big opening often enjoyed by a male-driven event pic or family movie.

No romantic comedy, of whatever rating, has opened to such numbers, prompting immediate talk of a sequel.

Nor was it a matter of Paramount’s “Crystal Skull” underperforming in its second sesh. The Steven Spielberg-directed tentpole, jumping the $200 million mark over the weekend, is tapping into the lucrative family market.

“Crystal Skull” declined a respectable 54% in its second frame to an estimated $46 million from 4,264 runs; cume is $216.9 million. While “Sex and the City” had an enormous Friday — $26.9 million — “Crystal Skull” beat out the romantic comedy on Saturday and is expected to have done the same on Sunday.

“Sex and the City” wasn’t the only title that did better than expected.

Rogue Pictures and Universal’s horror title “The Strangers” grossed an estimated $20.7 million from 2,467 runs in its debut, far exceeding expectations. Film, costing roughly $9 million to produce, was No. 3 for the weekend.

The frame was up as much as 31% over the same weekend last year, when “Knocked Up” opened.

Girl power

“This has become a cultural phenomenon. What this shows is that given the right project, you can create a frenzy for the female aud, just like we are used to with boys and men,” Warner prexy of domestic distribution Dan Fellman said.

The “Sex and the City” pic, reuniting the original cast four years after the HBO series went off the air, did just that. On Friday, a whopping 85% of the aud were female as women across the country planned en masse theater outings with their girlfriends; 80% of that number were over age 25. Film received an A CinemaScore.

Pic, playing in 3,285 runs, would have been considered a success had it matched the $27.5 million opening for summer 2006 B.O. hit “The Devil Wears Prada,” or last year’s $30.7 million debut for Judd Apatow’s R-rated laffer “Knocked Up.”

“Sex and the City” scored not only the top opening for R-rated comedy but the fifth best bow of all time for any R-rated film. Opening was also the best ever for a live-action adaptation of a TV series; the previous record-holder was “Mission Impossible,” which bowed to roughly $45 million.

Online ticket service Fandango reported that “Sex and the City” made its top 10 list of most advance ticket sales.

The question now is the pic’s playability. Film took a 33% dip from Friday to Saturday, reflecting the fact that many women went on the first day.

Fellman said he believes the romantic comedy will have strong legs and that it played somewhat like a date movie on Saturday, with more men in the aud. He said that’s an indication that more men will begin to see “Sex and the City.” He also pointed out that chick flicks do strong weekday numbers.

“We’re in very good shape,” Fellman said. “Now, I’m waiting for the sequel. And I think everyone else is too.”

Pic was directed by Michael Patrick King and stars Sarah Jessica Parker, Kim Cattrall, Kristin Davis, Cynthia Nixon and Chris Noth as “Mr. Big.”

“Sex and the City” marks New Line’s best box office showing in recent times, although New Line is no longer a standalone studio but a label within the Warner Bros. fold. Warners is distributing all New Line titles.

There’s other evidence of the box office might of women. Earlier this year, tween girls proved their B.O. power when turning Disney’s 3-D pic “Hannah Montana/Miley Cyrus: The Best of both Worlds Concert Tour” into a hit.

Trend situation

All told, five of the weekend’s top 10 movies are romantic comedies or female-skewing comedies: “Sex and the City,” 20th Century Fox’s “What Happens in Vegas,” Sony’s “Made of Honor” and U’s “Baby Mama” and “Forgetting Sarah Marshall.”

“What Happens in Vegas” saw the lowest week-to-week dip among the top 10 films, declining 25% in its fourth frame to $6.8 million from 3,806 runs. Cume is $66 million. Film is rated PG-13.

Universal prexy of domestic distribution Nikki Rocco said the R-rated “Strangers” provided the perfect counterprogramming. Film, starring Liv Tyler and Scott Speedman, placed No. 3 in its bow after “Sex and the City” and “Crystal Skull.”

Rocco said the film played strongly among both younger men and women.

Coming in No. 4 for the weekend was Paramount’s summer blockbuster “Iron Man,” which declined a slim 32% in its fifth frame to an estimated $14 million from 3,650; cume is $276.6 million.

Disney and Walden Media’s “The Chronicles of Narnia: Prince Caspian” was No. 5, declining an estimated 43% to $13 million from 3,801 for a cume of $115.7 million in its third frame.

Indie fare

On the specialty side, IFC Films’ “Savage Grace” nabbed a per location average of $12,078 as it debuted on two screens with an estimated gross of $24,156. Paramount Vantage’s “The Foot Fist Way” scored a per screen average of $9,003 as it debuted on four screens and grossed an estimated $36,102.

ThinkFilm’s “Stuck,” starring Mena Suvari and Stephen Rea, grossed an estimated $10,200 as it bowed in two theaters for a per screen average of $5,100.

In its second sesh, First Look’s political satire “War, Inc., toplining sibs John and Joan Cusack, grossed an estimated $24,210 from two theaters for a per screen average of $12,105 and cume of $78,714.