The French-directed black-and-white movie earned Oscars for best director for Michel Hazanavicius and best actor for Jean Dujardin, who played a silent movie era star whose career was torpedoed by the arrival of the "talkies."
"I love your country," Dujardin told the Hollywood audience as he accepted his Oscar, the first for a French actor, for his role as silent movie star George Valentin, whose career is torpedoed by the arrival of the "talkies."
After thanking the film's cast and crew -- adding to "my wife, I love you" -- he broke into French, using an expletive and then saying, "Great! Thank you very much!"
Martin Scorsese's 3D adventure "Hugo" -- which had the most nominations, with 11 compared to 10 for "The Artist" -- also ended the evening with five prizes, but all of them came in technical categories.
Meryl Streep won best actress for her powerful turn as former British premier Margaret Thatcher in "The Iron Lady," earning a standing ovation from the A-list Hollywood audience.
It was the third Oscar for the 62-year-old Streep and her first in three decades, underscoring her status as the pre-eminent actress of her generation.
"When they called my name, I had this feeling I could hear half of America going, 'Oh no. Come on ... Her, again?' You know. But, whatever!" she said, rolling her eyes.
Octavia Spencer took home the prize for best supporting actress for her role as a black maid in the civil rights drama "The Help," receiving a standing ovation for her powerhouse performance.
Veteran Canadian actor Christopher Plummer crowned a six-decade acting career with a long-overdue Oscar, a best supporting actor trophy for his role in "Beginners" as an ailing widower who embraces his homosexuality.
Kissing his coveted golden statuette, he joked: "You're only two years older than me, darling -- where have you been all my life?" adding that he had been rehearsing his Oscar acceptance speech since he was born.
Hollywood's biggest and most glittering night had long been expected to be a battle between "Hugo" and "The Artist," two odes to film-making.
Other winners included the Johnny-Depp voiced "Rango," which won the best animated feature prize, and Woody Allen, who was honored for best original screenplay for "Midnight in Paris."
In the foreign language category, Iran's "A Separation" beat films from Belgium, Canada, Israel and Poland as expected.
Its director Asghar Farhadi dedicated the award to Iranians "who despise hostility and resentment," and referred to current tension between Tehran and the West over the Islamic republic's suspect nuclear program.
Scorsese was not the only legendary director in the mix -- Allen was in the running for best picture honors for "Midnight in Paris," and Steven Spielberg gunned for the top prize with "War Horse."
Buddies George Clooney and Brad Pitt both lost out to Dujardin, who had already won a slew of awards for his turn as suave George Valentin.
Clooney had downplayed his hopes of winning best actor before the show, saying on the red carpet: "I have a feeling in the best actor race you're going to hear someone speaking French."
The show was presented by a galaxy of stars, including last year's best actress and actor Natalie Portman and Colin Firth, Tom Cruise, Penelope Cruz, Tom Hanks and Angelina Jolie.
Highlights included a breathtaking cinema-themed performance by Canadian dance troupe Cirque du Soleil, including rapid-fire acrobatics and tumbling across the stage and ceiling of the auditorium.
"Wow," said veteran host Billy Crystal, presenting the show for the ninth time. "I pulled a hamstring just watching that."
The spectacle had begun even before the curtain went up, with the usual procession of stars in glittering gowns on the red carpet leading into the Oscars, the climax of Hollywood's annual awards season.
British comic Sacha Baron Cohen also pulled a colorful stunt, coming dressed as the star of his latest movie, "The Dictator" -- and pouring the faux ashes of late North Korean leader Jim Kong-Il onto the red carpet.