Neeson's thriller, "Unknown," debuted as the No. 1 movie with $21.8 million, following in the footsteps of his 2009 action hit "Taken," according to studio estimates Sunday.
Another action tale, "I Am Number Four," opened at No. 2 with $19.5 million.
A Warner Bros. release, "Unknown" stars Neeson as a botanist who awakens from a coma to find his wife claims she does not know him and that another man has taken his identity.
DreamWorks' "I Am Number Four" stars Alex Pettyfer as a teenage alien refugee on Earth who develops superpowers to battle the evil invaders that destroyed his planet. It was the first DreamWorks movie released under the company's distribution deal with Disney.
While "I Am Number Four" held youth appeal, "Unknown" was a rare No. 1 film that did most of its business among older crowds. According to Warner, 54 percent of the movie's audience was 50 and over and 89 percent was 25 and over.
The 58-year-old Neeson has had action roles before but found unexpected success as an all-out action hero with "Taken," a $100 million hit.
"He's the new man. He's stepped up to the plate. Put him in the right role and he's every man's action star," said Dan Fellman, head of distribution at Warner.
Two movies that opened the previous weekend held the next two spots in the top 10.
Disney's animated comedy, "Gnomeo & Juliet," was No. 3 with $19.4 million, finishing so closely to "I Am Number Four" that the two movies could change rankings when studios release final numbers Tuesday, after the long President's Day weekend. "Gnomeo & Juliet" raised its total to $50.4 million.
Adam Sandler and Jennifer Aniston's romance "Just Go With It," which had been No. 1 the previous weekend, fell to fourth place with $18.2 million. The Sony release lifted its total to $60.8 million.
The weekend's other new wide release, Martin Lawrence's comedy, "Big Mommas: Like Father, Like Son," was No. 5 with $17 million. The 20th Century Fox sequel has Lawrence reprising his role as a federal agent who goes undercover as a hefty woman to crack a case.
Hollywood finally broke a long downturn in business during which revenues were off 14 straight weekends compared to last year's.
This weekend, receipts totaled $144 million, up 7.7 percent compared to the same period last year, according to box-office tracker Hollywood.com.
But compared to President's Day weekend in 2010, which fell a week earlier, revenues this time were down 30 percent.
"This was certainly not a record President's Day weekend by any stretch, but it was a good weekend," said Hollywood.com analyst Paul Dergarabedian. "It was solid but not spectacular, but at least it broke the down streak."
Two top contenders at next Sunday's Academy Awards hit the $100 million mark.
The Weinstein Co. drama "The King's Speech," the best-picture front-runner, pulled in $6.6 million to lift its total to $103.3 million. Fox Searchlight's psychosexual thriller, "Black Swan," took in $1.3 million and raised its haul to $101.5 million.
Colin Firth of "The King's Speech" and Natalie Portman of "Black Swan" are considered the favorites for the lead-acting Oscar awards.
Estimated ticket sales for Friday through Sunday at U.S. and Canadian theaters, according to Hollywood.com. Final figures will be released Tuesday.
1. "Unknown," $21.8 million.
2. "I Am Number Four," $19.5 million.
3. "Gnomeo & Juliet," $19.4 million.
4. "Just Go With It," $18.2 million.
5. "Big Mommas: Like Father, Like Son," $17 million.
6. "Justin Bieber: Never Say Never," $13.6 million.
7. "The King's Speech," $6.6 million.
8. "The Roommate," $4.1 million.
9. "The Eagle," $3.6 million.
10. "No Strings Attached," $3.1 million.
Universal Pictures and Focus Features are owned by NBC Universal, a unit of Comcast Corp.; 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.; 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.