The French-directed movie won best musical/comedy, best musical/comedy actor and best musical score, one more than family drama "The Descendants" which won two including best drama picture and best actor for George Clooney.
"We thought it would be a movie for the festivals, a film for critics ... but not this. We didn't expect this," said director Michel Hazanavicius, after being joined onstage by the movie's trick-performing dog star, Uggie.
Meryl Streep won best actress for her mesmerizing portrayal ofBritish prime minister Margaret Thatcher in "The Iron Lady," while best director went to Martin Scorsese for his 3D adventure "Hugo."
There was disappointment for civil rights movie "The Help," nominated for five awards but winning only one, as well as Brad Pitt's baseball-themed "Moneyball" and Clooney's political thriller "The Ides of March," which each had four nods but went home empty-handed.
But Clooney won big with "The Descendants," a Hawaii-based family drama which took the top prize at Hollywood's main pre-Oscars awards show, as well as best actor.
"Our quarterback was George Clooney," said "The Descendants" producer Jim Burke, accepting the award at the climax of the three-hour Globes show at the Beverly Hilton hotel in Los Angeles.
The movie missed out in the screenplay category to Woody Allen's "Midnight in Paris," was beaten for supporting actress by Octavia Spencer in "The Help," and best director where Scorsese won for "Hugo."
"The Artist," which had garnered the most Globes nominations with nods in six categories, was beaten for best director by Scorsese for "Hugo," for best supporting actress by Spencer and best screenplay by Allen's box office hit.
Billed as a tribute to the silent movie era, the film tells the story of silent star George Valentin (played by Dujardin) whose career is torpedoed by the arrival of the "talkies."
It won best film and best director at the New York Film Critics Circle awards in November, and more recently the Directors Guild of America (DGA) best picture seen as a key indicator for the Oscars, due on February 26.
It took yet another prize just three days before the Globes with the Critics' Choice best film award in Los Angeles on Thursday. After its Globes success, the Oscars nominees will be announced on January 24.
Other winners Sunday night included Michelle Williams as best actress in a musical or comedy for her Monroe turn in "My Week with Marilyn," and best supporting actor for Christopher Plummer in "Beginners."
Best animated feature went to Spielberg's big screen version of the Belgian cartoon book hero, "The Adventures of Tintin."
Best foreign language movie went to "A Separation" from Iran, which beat films from China and Belgium as well Spanish Pedro Almodovar's "The Skin I Live In," and Angelina Jolie's directoral debut, "In the Land of Blood and Honey."
"The Artist"'s first prize of the night was for best original score, for Ludovic Bource, who apologized, saying "I'm sorry, I'm French," before pulling out a piece of paper and reading his acceptance speech.
Taking up the theme Madonna, who won best original song a short time later, appeared to forget her words initially, saying: "This is a surprise," before adding, after a pause: "I'm not French, I have no excuse."
British comic Ricky Gervais, hosting for the third straight year despite ruffling feathers at last year's show, was again on provocative form although perhaps not quite as near-the-bone as 12 months ago.
"So, where was I?" he opened the show with, before taking an early stab at the Globes themselves.
"It's just like the Oscars without the esteem," he said, adding: "The Golden Globes are to the Oscars what Kim Kardashian is to Kate Middleton" to groans from the star-studded audience.
