It was a triumphant night for films dealing with homosexuality and transsexuality. Along with the victories for Brokeback Mountain, acting honors went to Felicity Huffman in a gender-bending role as a man preparing for sex-change surgery in Transamerica and Philip Seymour Hoffman as gay author Truman Capote in Capote.
"I know as actors our job is usually to shed our skins, but I think as people our job is to become who we really are, and so I would like to salute the men and women who brave ostracism, alienation and a life lived on the margins to become who they really are," Huffman said.
Director Lee's Brokeback Mountain, the story of two rugged Western family men (Heath Ledger and Jake Gyllenhaal) concealing their affair, has emerged as a front-runner for the Oscars - which occasionally have handed out top acting prizes for performers in homosexual or gender-bending roles but have never given the best-picture Oscar to a gay-themed film.
Oscar nominations come out Jan. 31, with the awards presented March 5.
Brokeback Mountain also won for best screenplay and song, "A Love That Will Never Grow Old."
Phoenix and Witherspoon won for best actor and actress in a movie musical or comedy for the biopic that follows country legend Cash's career and his long courtship with the love of his life, June Carter.
The Globe audience clapped along to Cash's song "I Walk the Line" as Phoenix took the stage.
"Who would ever have thought that I would win in the comedy or musical category?" said Phoenix, poking fun at his image for dark, brooding roles. "Not expected."
Phoenix, who did his own singing in the film, thanked "John and June for sharing their life with all of us."
"This film is really important to me," said Witherspoon, who offers a spirited performance and fine singing as Carter. "It's about where I grew up, it's about the music I grew up listening to, so it's very meaningful."
George Clooney, who was among the directing nominees for Good Night, and Good Luck, won the supporting-actor Globe for the oil-industry thriller Syriana, and Rachel Weisz earned the supporting-actress prize for the murder thriller The Constant Gardener.
Syriana spins a convoluted story of multiple characters caught up in a web of deceit, greed, corruption and power-brokering over Middle Eastern oil supplies. Clooney plays a fiercely devoted CIA undercover agent who comes to question his country's actions in the region.
Clooney thanked writer-director Stephen Gaghan for a movie "that asks a lot of difficult questions."
There are similar corporate undertones to The Constant Gardener, in which Weisz plays a humanitarian-aid worker whose husband (Ralph Fiennes) is drawn into a dogged investigation of business interests connected to her murder.
"I share this with Ralph Fiennes," said Weisz. "One couldn't ask for a more magical, ... committed actor."
Brokeback Mountain won the screenplay award for Larry McMurtry and Diana Ossana. McMurtry thanked his constant companion during the lonely process of writing.
"Most heartfelt, I thank my typewriter. My typewriter is a Hermes 3000, surely one of the noblest instruments of European genius," McMurtry said.
Television winners included Geena Davis for best drama series actress as the U.S. president in Commander in Chief, Hugh Laurie for drama series actor as a cranky, pill-popping doctor in House, and Steve Carell for best comedy series actor as an incompetent boss in The Office.
"This is really wonderful for a fledgling little show like ours," said Davis.
Mary-Louise Parker of Weeds beat out the four lead actresses of Desperate Housewives for best actress in a comedy series.
But Desperate Housewives did win for best musical or comedy series.
Lost was honored as best drama series.