The multiverse sci-fi epic, directed by Daniel Kwan and Daniel Scheinert, claimed seven prizes including three acting gongs, best directing and best picture, the biggest of the night.
It was a disappointing evening for Irish talent with The Banshees Of Inisherin going home empty-handed despite its nine nominations.
Yeoh claimed the Oscar for best leading actress, fending off competition from two-time Oscar winner Cate Blanchett to become the first woman from an Asian background to win the prize.
Taking to the stage, she said: “For all the little boys and girls who look like me, this is a beacon of hope and possibilities.
“Dream big, dreams do come true. Ladies, never let anyone tell you you are past your prime.”
She added: “This is history in the making.”
Speaking in the winners room later, she told reporters that she had “kung-fud” the “glass ceiling” with her win.
“I think this is something that we have been working so hard towards for a very long time and tonight we frigging broke that glass ceiling,” she said.
“I kung-fud it out and shattered it, and we need this because there are so many who have felt unseen or unheard.”
Yeoh’s co-star Jamie Lee Curtis, 64, won her first Oscar, for supporting actress, and paid tribute to all the special people in her life.
The actress, who is the daughter of Hollywood stalwarts Janet Leigh and Tony Curtis, added: “And my mother and father were both nominated for Oscars in different categories, I just won an Oscar.”
Kwan and Scheinert, jointly known as “The Daniels”, took home the award for best directing – only the third time it has gone to a duo.
Vietnam-born American star Ke Huy Quan received a standing ovation as he took to the stage after claiming best supporting actor for his role in Everything Everywhere All At Once, becoming the first person from an Asian background to win the category.
“My journey started on a boat,” he said. “I spent a year in a refugee camp and somehow I ended up here on Hollywood’s biggest stage.”
Brendan Fraser won the best actor Oscar for his performance as a reclusive English teacher with morbid obesity in The Whale, completing a dramatic career comeback after years out of the spotlight.
The Mummy actor, 54, was visibly emotional as he thanked director Darren Aronofsky for “throwing me a creative life-line”.
Costume designer Ruth E Carter became the first African-American to win two Academy Awards for best costume design – for her work on the first Black Panther film and now its sequel, Wakanda Forever.
All Quiet On The Western Front also enjoyed a successful night, continuing its runaway success at the Baftas last month, by securing four awards including best cinematography and original score.
The UK’s tally of four Oscars is the lowest since 2017, when the country came away with just a single award. Last year the UK won six.
The co-directors of An Irish Goodbye led a chorus of Happy Birthday for the film’s star James Martin from the stage after the film won best live action short film.
Baz Luhrmann’s Elvis failed to capitalise on its eight Oscar nominations, going home empty handed despite its star Austin Butler being touted as a favourite to take best actor.
Elsewhere on the night, Elizabeth Banks tripped as she took to the stage to present the award for best visual effects, which went to Avatar: The Way Of Water, but quickly managed to steady herself.
She was joined by a person wearing a bear costume in reference to her recent film Cocaine Bear and quipped: “Oh my God. He tripped me.”
John Travolta became emotional as he introduced an in memoriam segment which began with a tribute to his late Grease co-star Dame Olivia Newton-John.
The award for best documentary feature film went to Navalny, about Russian opposition leader Alexei Navalny and the events related to his 2020 poisoning.
Director Daniel Roher dedicated the award to Navalny and political prisoners around the world, saying: “Alexei, the world has not forgotten your vital message to the world.”
Navalny’s wife, Yulia Navalnaya, added: “Alexei, I am dreaming of the day you will be free and our country will be free, stay strong my love.”
Host Jimmy Kimmel kicked off the night by entering the stage attached to a parachute, in a nod to best picture nominee Top Gun: Maverick and made references to last year’s slap incident which involved Will Smith and Chris Rock.
In a departure from previous years, the Oscars swapped its usual red carpet for a champagne carpet, with stars including Bill Nighy and Cate Blanchett wearing a blue ribbon as part of an initiative from the United Nations refugee agency, the UNHCR.