"This is for anyone who has the faith and the courage to hold onto the goodness in themselves and to hold onto the goodness in each other, no matter how difficult it is to do that," Zhao said. "This is for you, you inspire me to keep going."
Kathryn Bigelow was the first woman to win, for "The Hurt Locker," in 2009.
This was the only year in Oscar history with two female nominees, Zhao and "Promising Young Woman" director Emerald Fennell. Only seven women have ever been nominated.
INTERACTIVE: How women are represented in Oscar nominations
It was the first Oscar for the 39-year-old Zhao, who was born in Beijing and went to college and film school in the United States. "Nomadland" is her third feature.
The other nominees were Lee Isaac Chung for "Minari," Thomas Vinterberg for "Another Round," and David Fincher for "Mank."
Zhao won her second Oscar of the night when "Nomadland" won best picture. She was also nominated for writing and editing. "Nomadland" was up for a total of six Oscars this year.
Zhao hit the red carpet earlier in the evening with Swankie, one of the real-life nomads featured in the film.
Asked if she is surprised to be a movie star, Swankie said: "I'm not a movie star. It's not my acting that's Oscar-worthy, it's more nomadic lifestyle that's Oscar-worthy.
"When you saw the monologues that she did in the film, what she represents and how she chooses to live her life, and her strengths, her resilience, her hope, it inspired all of us," Zhao said of Swankie's performance.
Zhao noted that she came up with several of her fellow nominees, adding that it's "really exciting to celebrate here in person."
The film, which is based on a 2017 book by Jessica Bruder, tells the story of a Fern (Frances McDormand), a laid-off widow on a journey to survive and search for her purpose. Fern meets up with a community of drifters as she makes her way across the American West, working odd jobs while living out of her van.
McDormand, who optioned Bruder's book with Peter Spears in 2017 and is also credited as a producer on the film, approached Zhao after seeing her 2017 film "The Rider." They worked together to build out and personalize the Ford Econoline van that serves as Fern's home in the film.
"I was actually in the process of building a van because of the amount of time I slept in my Subaru making my first two films, but I wasn't really aware of the extent to which people gathered together and followed this life," Zhao explained in production notes from Searchlight Pictures.
Many of those whom Zhao cast as nomads in the film are real-life nomads, with only a handful of professional actors in featured roles.
"Chloé immerses herself in her subjects' life narratives and looks for 'the hook' that gives her the dramatic arc for a film," McDormand said of working with Zhao. "Our process on 'Nomadland' was a challenge for both of us because we were imposing the hybrid of non-professionals from the nomad community and David Strathairn and I as professionals acting our roles."
"Nomadland" won four prizes, including best picture, at the British Academy Film Awards, earlier this month, as well as the top award at the 32nd annual Producers Guild of America Awards. Zhao took top honors at the 73rd annual Directors Guild Association Awards. It also won best drama film at the Golden Globes.
MORE: Full list of Academy Awards winners
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The Associated Press contributed to this report.