[10] Chan made her stage debut in the British premiere of Bertolt Brecht's last play, Turandot, at the Hampstead Theatre, London, in 2008.

[11] Chan appeared in the autumn 2009 special of the BBC's Doctor Who, titled "The Waters of Mars", playing geologist Mia Bennett.

[17][18] Chan's first major role came in 2010,[19] as a heavily accented Chinese immigrant appearing in The Blind Banker, a first series episode of BBC's Sherlock.

[19][20] Chan's next releases, Pimp, (2010) and Shanghai (2010), were panned by critics, while Submarine premiered at the 35th Toronto International Film Festival to positive reviews.

[24] Later that year, she appeared in Channel 4's Fresh Meat[25] and made a film for Amnesty International to celebrate the 60th anniversary of the Universal Declaration of Human Rights.

[6] In 2012, Chan appeared in Bedlam,[26] True Love, a five-part semi-improvised television series produced by Working Title,[27] and the British premiere of Yellow Face by American playwright David Henry Hwang at The Park Theatre, London.

She received rave reviews with Michael Billington of The Guardian writing, that "Chan shows, with great skill...a coolly inscrutable Ruth".

"[41] That same year she portrayed the protagonist's girlfriend, Chen-Lin, in French comedy-drama Belles Familles (2015), which was released at the 2015 Toronto International Film Festival.

[49] In 2018, Chan joined Andrea Riseborough, Jane Horrocks, Jaime Winstone, and Laura Carmichael to star in a film produced by ActionAid, encouraging the British public to support girls at risk of sexual violence.

[59] Chan portrayed Elizabeth Hardwick in Josie Rourke's directorial debut, historical drama Mary Queen of Scots (2018), which premiered at the AFI Fest.

[64][65] That same year, she was one of fifteen women selected to appear on the cover of the September 2019 issue of British Vogue, by guest editor Meghan, Duchess of Sussex.

[69] That same year, Chan was the fifteenth recipient of the Women In Film Max Mara Face of the Future award, given for her "distinguished acting achievements" and "personal embodiment of timeless style and grace".

[70] Chan voiced the warrior princess Namaari, the antagonist of the Disney animated film Raya and the Last Dragon, which premiered in March 2021.

[87] In response to the xenophobic and racist attacks against people of East and Southeast Asian descent during the COVID-19 pandemic, Chan advocated for the #StopAAPIhate movement and fundraising campaign.

[88][89] In May 2021 Chan launched the #StopESEAHate campaign to assist people of East and Southeast Asian descent who are victims of hate crimes.

The following year, she attended the 91st Academy Awards wearing a fuchsia pink Valentino dress, which gained significant media attention and praise from critics.

[99] Other notable fashion appearances of Chan include the Captain Marvel premiere in 2019, where she wore custom Ralph & Russo; the 2019 Vanity Fair Oscar party, styled by Tom Ford and Jimmy Choo; the 2019 Critics' Choice Awards, dressed by Jason Wu; the 2019 Golden Globes, where she wore a Valentino couture hybrid gown; among several others through the years.

[101] Continuing her partnership with Louis Vuitton, Chan's custom archival-inspired black dress from the 2022 In America-themed Met Gala was praised among the "best-dressed" of the night.

Chan also wore Louis Vuitton to the 2023 Vogue World event, with a custom "organza dress covered in bluish silver paillettes".

[108] In 2024, Chan was featured in Edward Enninful's final British Vogue cover, titled "40 Megastars, One Magnificent Image", appearing alongside forty notable female celebrities including Miley Cyrus, Jane Fonda, Kaia Gerber, Salma Hayek, Dua Lipa and Oprah Winfrey.

Examples of Asian designers Chan has worn at public events include a couture chiffon Miss Sohee gown accompanied by Anabela Chan jewellery at the Newport Beach Film Festival in February 2023; a strapless pink Jason Wu gown to an event by George and Amal Clooney; a flower-style Oscar de la Renta dress by "Slaysian" creative director Laura Kim;[110] at the 2022 Cannes Film Festival; among multiple others.

[114] In September 2013, Chan appeared at the Old Bailey in central London as a witness to a fatal stabbing outside Putney Bridge tube station.

[115] Chan and her partner Dominic Cooper participated in the People's Vote March, expressing support for a second Brexit referendum, in October 2018.