"Interstellar," starring Matthew McConaughey, opened on Wednesday and recorded $50 million over the three days from Friday through Sunday, and $52.2 million over its five-day run.
If the final figures hold up, it would be only the fourth time in history that two new films had hit the $50 million mark on the same debut weekend, the last time being June 2013 with "Monsters University" and "World War Z," box office tracking firm Rentrak said.
"Gone Girl," director David Fincher's hit starring Ben Affleck as a husband suspected of murdering his wife, was third with $6.1 million, according to estimates from Rentrak. It has taken in more than $145 million since opening on Oct. 3.
Inspired by a Marvel comic of the same name, "Big Hero 6" is set in a fictional futuristic metropolis called Sanfransokyo, in which a 14-year-old computer whiz kid fashions a team of superheroes out of students from a university robotics lab.
With the help of a waddling, 6-foot-tall (183-cm) personal healthcare robot called Baymax, the team defeats a masked villain who harnesses the power of microbots to wreck havoc on the city.
Dave Hollis, Walt Disney Studios' head of distribution, said the film got "a great response from kids, from parents and from non-parents," adding "you need to transcend the family audience in order to a get a number like this."
With the film "delivering general audience segments ... we're set up to do a great, long run," Hollis added.
"Interstellar," co-starring Anne Hathaway, features a team of space travelers who move through a wormhole in search of a habitable planet after blight and dust storms render Earth unlivable. Made for $165 million, the film was financed by Warner Brothers, Paramount and Legendary Pictures.
The film's $13.4 million from large-format IMAX screens set a record for a November opening, as well for the biggest percentage of the total take for a first-run release.
Initially linked to director Steven Spielberg, Paramount turned the film over to Nolan after Spielberg struck a deal with Disney in 2009. British-born Nolan brought a huge following from sci-fi and comic book fans from his successes with the "Dark Knight" Batman films and "Inception."
"Audiences love original movies and concepts," said Megan Colligan, president of worldwide marketing and distribution at distributor Paramount Pictures, a unit of Viacom Inc.
"It's become sort of an event movie, with people planning for it and buying their tickets in advance," said Colligan.
She added that the studio would be focusing its marketing in the coming weeks toward "Interstellar"'s spectacle aspect to draw in families and younger men with the intent of sustaining its box office performance through the Thanksgiving holiday.
Rounding out the top five, low-budget "Ouija," the top film for the past two weeks, made $6 million while the Bill Murray-Melissa McCarthy comedy "St. Vincent" was No. 5 with $5.7 million.
"Gone Girl" was distributed by 20th Century Fox, the film studio owned by 21st Century Fox. Comcast Corp's Universal Pictures released "Ouija". "St. Vincent" was released by the privately held Weinstein Company.