Comer gained recognition for appearing in the series My Mad Fat Diary (2013–2015) and Doctor Foster (2015–2017), and starred in the drama miniseries Thirteen (2016).

[4][5][6] At the age of 11, she started acting at a weekend drama school called CALS in the Belle Vale area of Liverpool.

[10] Although she did not win, her performance prompted her drama teacher to call in a favour from friends in the entertainment industry, allowing her to audition for a BBC Radio 4 play.

[17][18][19] Her first starring role was in 2016 as Ivy Moxam in the BBC Three miniseries Thirteen, which earned her a nomination for the British Academy Television Award for Best Actress.

[20] In November 2016, she appeared in the BBC One miniseries Rillington Place as Beryl Evans, one of serial killer John Christie's victims.

[10] The same year, Comer was listed as one of Screen International's "Stars of Tomorrow" in association with the BFI London Film Festival.

[22] Also in 2017, Comer made her feature film debut, as Christine in the Morrissey biographical drama England Is Mine, directed by Mark Gill.

[29] After the first season of Killing Eve aired, Comer revealed how much she'd learned from embodying her character, stating: "I had this impression that, to do good acting, everything is minimal, really whispered, less is more.

[38] In April 2019, Comer revealed she had been forced to drop out of Kenneth Branagh's 2022 adaptation of Agatha Christie's Death on the Nile due to scheduling conflicts.

[40][41][42] In June 2020, Comer played the lead role of Lesley in a BBC iPlayer reboot of the Talking Heads episode "Her Big Chance" (filmed in lockdown due to the COVID-19 pandemic).

[49] Later in 2021, Comer teamed with writer Jack Thorne and actor Stephen Graham to star in the Channel 4 drama Help, as a young care home worker struggling during the early days of the COVID-19 pandemic in the United Kingdom; she also served as an executive producer.

[51] Also in 2021, Comer portrayed Marguerite de Carrouges in Ridley Scott's The Last Duel, alongside Ben Affleck, Matt Damon and Adam Driver.

[52][53][54] Comer made her West End debut in Suzie Miller's one-woman play Prima Facie at the Harold Pinter Theatre which started in April 2022 and concluded in June 2022.

[67] In 2023, Comer starred, alongside Austin Butler and Tom Hardy, in Jeff Nichols's The Bikeriders, a drama inspired by the photography of Danny Lyon and his 1967 book of the same name.

[68] She subsequently starred in and produced the environmental thriller The End We Start From, an adaptation of Megan Hunter's debut novel, directed by Mahalia Belo.

[80][81][82] She will also star, alongside Hugh Jackman, in Michael Sarnoski's upcoming action film The Death of Robin Hood.

[92][93][94] In September 2019, Comer was named the face of the Loewe spring/summer 2020 fashion campaign, which saw her star in a short film for the brand.

"[75] Sharing some insight towards her approach to relationships in 2020, Comer confided to British Vogue: "I think love's the best ... and [I] just kind of [go] with the flow and [do] my thing ...