Zhao was born in Beijing as Zhao Ting. In an interview with Vogue in 2018, she said that her parents sent her to "one of those Hogwarts boarding schools" in the UK where she learned English. She eventually finished high school in Los Angeles, living alone in Koreatown. Upon graduation, Zhao moved to Massachusetts to study political science at Mount Holyoke, a private liberal arts women's college before heading off to study film in New York.

After finishing her undergraduate studies, Zhao enrolled in the Graduate Studies film programme at New York University. During her studies, she made her first-ever film, the short film, Daughters, which nabbed the Best Student Live Action Short at the 2010 Palm Springs International ShortFest as well as the Special Jury Prize in the 2020 Cinequest Film Festival.

She shot her thesis and debut feature film, Song My Brother Taught Me (2015), a Native American drama in which she collaborated with fellow film student and partner, Joshua Hames Richards. The movie was critically praised and even received a nomination for the Independent Spirit Awards for Best First Feature. It also enjoyed a premiere at the Sundance Film Festival.

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On her venture into film after studying politics, Zhao said to Tatler: "When I was in college, I wanted to understand a lot of the things about America [that] I didn't quite understand when I first got here. And then it took me a couple of years just doing nothing much in New York, just working odd jobs, to realise that I have to do something with my life. That's how a lot of people ended up in film school."

Before Nomadland, Zhao's debut, Songs My Brothers Taught Me, upon premiering at Sundance Film Festival, later played at Cannes Film Festival as part of the Director's Fortnight selection. She followed up her debut with The Rider (2017), a drama that follows a young cowboy's journey to self-discovery after an accident ends his career. The movie premiered at the Cannes Film Festival and won the Art Cinema Award. This later earned Zhao nominations for Best Feature and Best Director at the 33rd Independent Spirit Awards.

Three years later, Zhao directed Nomandland, which premiered at the Venice International Film Festival to critical acclaim, with Zhao winning the Golden Lion award and then the People's Choice Award at the 2020 Toronto International Film Festival. She also won Best Feature and the Gotham Audience Award at the Gotham Awards.

For her win as Best Director at the Golden Globes, she is not only the second female director to nab the prize but she's also the first woman of Asian descent to be honoured.

According to Variety in February 2021, Zhao has surpassed Alexander Payne as the most awarded person in a single awards season in the modern era with 34 awards season trophies for directing, 13 for screenplay and nine for editing.

Nomadland also won Best Picture at the Golden Globes and is tapped to be an Oscar frontrunner.

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Influenced by Japanese manga which she described as her "first love" during an interview with Tatler, Zhao's next project is Eternals. She has been a fan of the Marvel Cinematic Universe "for the last decade" and has been vocal about wanting to create a Marvel movie. It seems like her dream has come true.

The movie is set to release in November and is based on the Marvel comic series of the same name. While her previous films have been mostly indie projects, Eternals is set to be her biggest one yet with its star-studded cast including Angelina Jolie, Salma Hayek, Kumail Nanjiani, Kit Harrington, Gemma Chan and Ma Dong-seok. But given Zhao's manga influences, the project shouldn't come as a surprise. She said that she always "wanted to be a manga artist" but "wasn't very good at drawing".

Other than Eternals, it was announced in 2018 that Amazon Studios has given the greenlight to Zhao's upcoming biopic on Bass Reeves, the first black US Deputy Marshal. No release date is announced but Zhao is set to direct and write the screenplay.

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For the most part, Zhao's films are mostly based in the US with themes of saying goodbye, finding a home or a sense of self. But she said that besides her own experiences growing up, "universal human struggles that we deal with" are the stories that she's drawn to. Leaving her home in China, studying abroad to eventually residing in the US, Zhao wants her stories to be something that people can connect with or relate to no matter where they're from.

"I think about my family back home in China a lot. And I didn't want to make a film where they go, 'Well, that's their problem. That has nothing to do with me". I think in that case, having my home in both countries, has made me think about both audiences. And they are quite different in many ways, and then they're similar in other ways. So I have to constantly think about serving both of them. That keeps me very, very disciplined. Telling a universal story," she tells Tatler.

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