Sunday's awards ceremony also opened wide to embrace the long-admired Jeff Bridges, who took best dramatic-acting honors for the country-music film "Crazy Heart," and a sitcom actress, Mo'Nique, who emerged as a fierce screen presence in "Precious."
Fox's spunky new TV musical comedy series "Glee" was honored, while the best TV drama award went to AMC's 1960s Madison Avenue saga "Mad Men" for the third year in a row.
Cameron was the big winner on the movie side, claiming best drama and best director for his science-fiction blockbuster and setting him for a possible awards sequel to 1997's "Titanic." Cameron's epic about the doomed oceanliner won the same prizes and went on to dominate the Academy Awards.
This time, though, instead of being "king of the world," as Cameron declared at the Oscar ceremony, he has become king of a computer-generated distant moon that made critics gush and sent box-office receipts soaring. The film has grossed $1.6 billion worldwide, second only to "Titanic" with $1.8 billion.
"'Avatar' asks us to see that everything is connected, all human beings to each other, and us to the Earth. And if you have to go four and a half light years to another, made-up planet to appreciate this miracle of the world that we have right here, well, you know what, that's the wonder of cinema right there, that's the magic," Cameron said.
Other film acting prizes went to Sandra Bullock for the football tale "The Blind Side," Meryl Streep for the Julia Child story "Julie & Julia," Robert Downey Jr. for the crime romp "Sherlock Holmes" and Austrian actor Christoph Waltz as a gleefully bloodthirsty Nazi in "Inglourious Basterds."
Sunday's winners could get a last-minute boost for the Oscars, whose nominations balloting closes Saturday. Last year's big Globe winner, "Slumdog Millionaire," went on to garner Oscar glory.
Michael C. Hall won for best actor in a TV drama for Showtime's "Dexter," in which he plays a serial killer with a code of ethics, targeting only other murderers. Hall's publicists said last week that Hall is being treated for Hodgkin's lymphoma and that the cancer is in remission.
"Dexter" also won the supporting-actor TV honor for John Lithgow. Other TV winners included Juliana Margulies as best actress in a drama for CBS' "The Good Wife" and Toni Collette as best comedy actress for Showtime's "The United States of Tara."
Bridges, a beloved veteran generally overlooked for key Hollywood honors, got a standing ovation at the ceremony hosted by Ricky Gervais.
"You're really screwing up my underappreciated status here," Bridges said.
The son of late actor Lloyd Bridges, Bridges thanked his father for encouraging him to go into show business.
"So glad I listened to you, dad," he said.
Bullock cited Michael Oher, the Baltimore Ravens rookie lineman whose life is the subject of "The Blind Side." She plays a wealthy Memphis woman whose family took the teenage Oher and gave him shelter after discovering he was homeless.
"If I may steal from Michael Oher, I may not be the most talented, but I've been given opportunity," Bullock said.
The Vegas bachelor bash "The Hangover" won for best musical or comedy, bringing uncharacteristic awards attention for broad comedy, a genre that often gets overlooked at Hollywood honors. The Globes marked a dramatic turning point for Mo'Nique, who was mainly known for lowbrow comedy but startled audiences with her brutal performance in "Precious: Based on the Novel `Push' By Sapphire," directed by Lee Daniels and starring newcomer Gabourey Sidibe, who was a Globe nominee.
Streep's competition for best actress in a musical or comedy included herself. She also was nominated for the romance "It's Complicated."
"I just want to say that in my long career, I've played so many extraordinary woman that I'm getting mistaken for one," Streep said. "I'm very clear that I'm the vessel for other people's stories and other people's lives."
The blockbuster "Up" came away with the award for animated film. Pixar Animation, the Disney outfit that made "Up," has won all four prizes for animated movies since the Globes introduced the category in 2006. Past Pixar winners are "WALL-E," "Ratatouille" and "Cars."
"Up" features the voice of Ed Asner in a tale of a lonely, bitter widower who renews his zest for adventure by flying his house off under helium balloons to South America, where he encounters his childhood hero and a hilarious gang of talking canines.
Jason Reitman and Sheldon Turner won the screenplay honor for "Up in the Air," which Reitman also directed. The foreign-language honor went to "The White Ribbon," a stark drama of guilt and suspicion set in a German town on the eve of World War I.
The rain-drenched red carpet was a rare sight for an awards show in sunny southern California, stars in their finery getting damp under umbrellas as storms swept the region.
Although the Globes are one of Hollywood's biggest parties, the ceremony included somber reminders of tragedy in the real world, many stars wearing ribbons in support of earthquake victims in Haiti.
The Globes, which aired on NBC, are presented by the Hollywood Foreign Press Association, a group of about 90 reporters covering show business for overseas outlets.