Hollywood actor Leo trumped British hopeful Eddie Redmayne for the best male actor award for his performance as a fur trapper in revenge epic The Revenant.
He was hugged by his Titanic co-star Kate Winslet on his way up to the stage, where he said: "I am truly humbled by this because it comes from my fellow actors.
"When I was 15 I was lucky enough to get a film called This Boy's Life and after that I watched as many films as I could and it gave me a such a respect for this craft.
"I was in awe of the performances and I was inspired. To any young actors, I encourage you to watch the history of cinema because we stand on the shoulders of giants."
He added: "My parents, thank you for listening to an overly ambitions, slightly annoying 13-year-old kid who wanted to go on auditions after school, I would not be here without you."
Brie Larson was presented with the award for outstanding performance by a female actor in a leading role for Room.
Addressing the members of the guild, she said: "When I was born I was worried I was unlovable and your movies made me feel less alone and made me feel it was a safe place to explore my creativity."
"We made a film about real people and real lives," he said in his acceptance speech at the Shrine Auditorium. "Thank you for giving this film some love."
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