The Warner Bros. sports tale had been runner-up for the previous two weekends to Summit Entertainment's vampire romance "New Moon," which fell to second place with $15.7 million.
Great word-of-mouth from fans has sustained "The Blind Side," which stars Sandra Bullock as a woman whose family adopts homeless teen Michael Oher, now a rookie tackle for the Baltimore Ravens.
"How outstanding is it to have a movie at No. 1 in its third weekend?" said Jeff Goldstein, executive vice president for distribution at Warner, who added that the movie so far has done more than double the business he expected. "I don't know of anybody who ever saw anything this big."
"New Moon" still is far ahead in total gross with $255.6 million domestically, compared to $129.3 million for "The Blind Side." Overseas, "New Moon" added $40.7 million to raise its international total to $314.5 million and its worldwide gross to $570.1 million.
"The Blind Side" and "New Moon" fended off a rush of new wide releases that had so-so to abysmal openings.
The nationwide debuts were overshadowed by a huge premiere in limited release for George Clooney's comedy "Up in the Air," which took in nearly $1.2 million at just 15 theaters for a whopping average of $79,000 a cinema.
Directed by Jason Reitman ("Juno"), Paramount's "Up in the Air" has earned great reviews and buzz as a potential Academy Awards front-runner, positioning it for a long run in theaters as it expands nationwide over the next few weeks. Clooney plays a corporate hit man addicted to the frequent-flyer life as he travels the country firing people for downsizing companies.
Lionsgate's war-on-terror-themed drama "Brothers" debuted at No. 3 with $9.7 million, averaging $4,646 in 2,088 theaters. A remake of a 2004 Danish film, "Brothers" stars Tobey Maguire, Natalie Portman and Jake Gyllenhaal in the story of a prisoner of war who returns from Afghanistan to find his sibling has become the man of the house for his family.
Sony's heist thriller "Armored," with Matt Dillon and Laurence Fishburne, premiered with $6.6 million and tied for No. 6, averaging $3,446 in 1,915 theaters.
Another foreign-language remake - Miramax's "Everybody's Fine," with Robert De Niro, Drew Barrymore and Kate Beckinsale in an update of a 1990 Italian film - opened a weak No. 10 with $4 million for an average of $1,888 in 2,133 cinemas. De Niro plays a retiree on a journey to reconnect with his grown children.
The vampire mania over "New Moon" did not extend to Full Circle Releasing's bloodsucker comedy "Transylmania," which took in just $274,000 in 1,007 theaters for a dismal average of $272. The movie is a campus-horror spoof about students studying at a Transylvania college overrun by vampires.
Overall revenues came in at $101 million, up 22.6 percent from the same weekend last year, when "Four Christmases" was No. 1 with $16.8 million.
Paul Dergarabedian, box-office analyst for Hollywood.com, estimates domestic receipts will finish at $10.6 billion for the year, easily surpassing the industry's all-time high of $9.68 billion in 2007.
Revenues stand at $9.66 billion after this weekend, so Hollywood should break that 2007 record in the next couple of days, Dergarabedian said.
With big movies such as James Cameron's sci-fi epic "Avatar" opening Dec. 18 and Robert Downey Jr.'s crime saga "Sherlock Holmes" and the family comedy "Alvin and the Chipmunks: The Squeakquel" arriving Christmas week, that $10.6 billion estimate for the year might prove conservative, Dergarabedian said.
"It will probably go higher if we consistently outperform the way we have been," Dergarabedian said.
Estimated ticket sales for Friday through Sunday at U.S. and Canadian theaters, according to Hollywood.com. Final figures will be released Monday.
1. "The Blind Side," $20.4 million.
2. "The Twilight Saga: New Moon," $15.7 million.
3. "Brothers," $9.7 million.
4. "Disney's a Christmas Carol," $7.5 million.
5. "Old Dogs," $6.9 million.
6. "Armored" (tie), $6.6 million.
6. "2012" (tie), $6.6 million.
8. "Ninja Assassin," $5 million.
9. "Planet 51," $4.3 million.
10. "Everybody's Fine," $4 million.
On the Net:
Box Office, http://www.hollywood.com/boxoffice
Universal Pictures and Focus Features are owned by NBC Universal, a unit of General Electric Co.; Sony Pictures, Sony Screen Gems and Sony Pictures Classics are units of Sony Corp.; Paramount and Paramount Vantage are divisions of Viacom Inc.; Disney's parent is The Walt Disney Co.; Miramax is a division of The Walt Disney Co.; 20th Century Fox, Fox Searchlight Pictures and Fox Atomic are owned by News Corp.; Warner Bros. and New Line are units of Time Warner Inc.; MGM is owned by a consortium of Providence Equity Partners, Texas Pacific Group, Sony Corp., Comcast Corp., DLJ Merchant Banking Partners and Quadrangle Group; Lionsgate is owned by Lions Gate Entertainment Corp.; IFC Films is owned by Rainbow Media Holdings, a subsidiary of Cablevision Systems Corp.; Rogue Pictures is owned by Relativity Media LLC; Overture Films is a subsidiary of Liberty Media Corp.