The Malaysian-born actor became the first Asian woman to win an Oscar for best actress for her multifaceted performance in the multiversal "Everything Everywhere All at Once."
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"Thank you for all the little boys and girls who look like me tonight," she said. "This is proof that dreams do come true. And ladies, don't let anyone ever tell you you're past your prime."
Michelle Yeoh's mother cried for joy for her "little princess" while watching from Kuala Lumpur, Malaysia.
"I so love my daughter and she has made Malaysia proud," Yeoh told a news conference, praising the actor as intelligent and hardworking daughter. "Malaysia Boleh (Malaysia Can)!"
Yeoh's victory comes almost 90 years after Luise Rainer, a white actor, won the same category for donning "yellowface" to play a Chinese villager in "The Good Earth."
As a nominee, Yeoh was the first in the category who identified as Asian. Merle Oberon, who was nominated in 1935 for "The Dark Angel" but didn't win, hid her South Asian heritage, according to birth records.
WATCH: Asians making history in Hollywood ahead of Oscars
Asians making history in Hollywood ahead of Oscars
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Yeoh beat out past Oscar winner Cate Blanchett ("Tár"), as well as Michelle Williams ("The Fabelmans"), Ana de Armas ("Blonde") and Andrea Riseborough ("To Leslie").
The category also received notice for who wasn't nominated: In a year of strong performances from Black women like Viola Davis ("The Woman King") and Danielle Deadwyler ("Till"), they were shut out. Meanwhile some criticized the grassroots campaigning by A-listers on social media for Riseborough.
Yeoh appeared a lock after winning seemingly every award everywhere, including the Golden Globe and Screen Actors Guild award, for her nuanced portrayal of Evelyn, an immigrant Chinese wife, mother and laundromat operator bracing for a tax audit.
"Everything Everywhere All at Once" took home 7 Oscars in total out of 11 nominations, including statues for best picture, best director, best film editing, best original screenplay, and best supporting actor and actress awards for Ke Huy Quan and Jamie Lee Curtis.
Yeoh got her start in the kung fu cinema world but rose to stardom in 1992 as Jackie Chan's co-star in "Supercop." American audiences got to know her even better over the next decade with hits like "Tomorrow Never Dies" and Ang Lee's "Crouching Tiger Hidden Dragon."
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When she first read the script for "Everything Everywhere," Yeoh thought it was "an independent film on steroids." She was ultimately swayed by the opportunity to give voice to immigrant mothers and grandmothers who go unnoticed. The multiverse movie was also a showcase across a bevy of genres - drama, comedy, sci-fi and fantasy.
At 60, Yeoh has been heavily in demand since her standout turn as a controlling matriarch in "Crazy Rich Asians." From there, she has done everything from a "Star Trek" spinoff to Marvel's "Shang-Chi and the Legend of the Ten Rings."
Yeoh will be seen later this year in the Disney+ series "American Born Chinese." She is also preparing to reunite with "Crazy Rich Asians" director Jon M. Chu for the screen adaptation of the musical "Wicked."
The Associated Press contributed to this report.