Nomadland, a recession-era tale about a community of van dwellers in the American West, has won the Oscar for best picture while Frances McDormand and Anthony Hopkins have taken out best actress and actor.
British actor Hopkins won his second Oscar for his heart-wrenching performance as a man with dementia in The Father.
The 83-year-old has a six-decade film, TV and stage career but is perhaps best known for playing the brilliant but twisted murderer Hannibal Lecter in the 1991 thriller The Silence of the Lambs, for which he won his first Oscar.
His best lead actor win makes him the oldest actor to get an Academy Award, an honor previously held by the late Christopher Plummer.
Nomadland featured McDormand as a widow in a depressed Nevada mining town who turns her van into a mobile home and sets out on the road, taking seasonal jobs and making friends along the way.
Directed by China native Chloe Zhao, it was widely considered front-runner heading into Hollywood's biggest night, having dominated this year's awards season.
The film is based on a 2017 nonfiction book by Jessica Bruder and features real-life nomads in supporting roles as fictionalised versions of themselves.
It's the second best actress Oscar for McDormand, who also won in 2018 for Three Billboards Outside Ebbing, Missouri.
China native Chloe Zhao was earlier named best director in a historic win making her the first Asian woman and only the second woman to take home the trophy.
Youn Yuh-jung won the best supporting actress Oscar for her role as a cantankerous grandmother in immigrant tale Minari.
Youn, 73, is the first South Korean actor or actress to win an Oscar in what is shaping as a milestone night for people of colour, as well as a return to glamour and in-person celebrations after a year of virtual ceremonies.
"Me being here, I cannot believe it," Youn said. She joked about people mispronouncing her name, adding, "Tonight you are all forgiven."
Zhao, 39, won for Nomadland about the travelling van community in modern America. She called making the film a "crazy, once-in-a-lifetime journey".
It has been 11 years since Kathryn Bigelow became the first woman to win the director Oscar, for Iraq war drama The Hurt Locker.
Zhao's win added momentum to an expected best picture win for Nomadland later on Sunday.
Zhao, who now lives in the United States, recalled growing up in China, where she came to believe "people at birth are inherently good".
"This is for anyone who has the faith and the courage to hold on to the goodness in themselves ... and in each other," she added.
Britain's Daniel Kaluuya was named best supporting actor for his role as 1960s Black Panther activist Fred Hampton in Judas and the Black Messiah.
The movie Soul, the first from Pixar to feature a black lead character, won best animated feature.
Social distancing forced a rethink of the ceremony, moving it to Union Station in downtown Los Angeles.
After strict COVID-19 testing and quarantine protocols, most celebrities were not wearing masks and were shown chatting in an outdoor courtyard ahead of the ceremony, which took place on a nightclub-style set inside the Mission Revival-style train station.
Celebrities were delighted to be back together in the same room.
"It's an amazing party! I was surprised. We haven't had that," Margot Robbie told reporters before the show began.
The Australian's production company, LuckyChap Entertainment, earned recognition as backer of Promising Woman, whose British writer and director, Emerald Fennell, won the first Oscar of the night for best original screenplay.
Australian Associated Press