Mendes' "1917" trumped big Netflix projects "The Irishman", "Marriage Story" and "The Two Popes", and Warner Bros. blockbuster "Joker".
"This is a huge, huge thing for this movie," said Mendes as he accepted the honour of Best Motion Picture - Drama.
"It opens in a week, wide. It's difficult to make movies without big movie stars in the leads and get people to come and see it in a cinema, and I really hope this means people will turn up and see it on the big screen, for which it was intended,a he added.
The DreamWorks Pictures war drama tells the story of two young British soldiers at the height of the war. It stars George MacKay as Lance Corporal Schofield and Dean-Charles Chapman as Lance Corporal Blake who are given an impossible task to deliver a message deep in the heart of enemy territory that, if successful, would save the lives of 1,600 British soldiers. Anil D. Ambani-led Reliance Entertainment will be releasing "1917", in India later this month.
It was a double bonanza for Mendes, who also picked up Best Director - Motion Picture award.
He beat Bong Joon-ho ("Parasite"), Todd Phillips ("Joker"), Martin Scorsese ("The Irishman") and Quentin Tarantino ("Once Upon a Time in Hollywooda) to win the accloade.
"Goodness, me. That is a big surprise. Thank you very much," the director said.
He honoured legendary Martin Scorsese while accepting the award.
"There's not one director in this room, not one director in the world, that is not in the shadow of Martin Scorsese. I just have to say that," he said.
Mendes, who earlier won won the Golden Globe for best director in 1999 for "American Beauty", dedicated the honour to his grandfather Alfred Mendes.
"I'd like to dedicate this to my grandfather," Mendes said, adding: "He signed up for the first world war, he was age 17. And I hope he's looking down on us. And I fervently hope it never, ever happens again. Thank you very much."
The director had a special mention for his wife Alison Balsom, as well as the "extraordinary young actors" and producers of the film.
( With inputs from IANS )