Poots first appeared on-screen in an episode of Casualty and had a non-speaking role in V for Vendetta, but she was largely unknown when, at the age of 17, Juan Carlos Fresnadillo cast her in the horror film 28 Weeks Later. Since then, she has appeared in films such as Cracks, Centurion, and as the female lead in the 2011 remake of Fright Night alongside Anton Yelchin. Although Poots has never formally trained as an actress, according to Giles Hattersley, she developed her acting skills through a practical apprenticeship that may have served her well, as she is "compellingly natural" in front of the camera.
In 2011, she was chosen by fashion house Chloé to appear in a campaign for its eponymous fragrance shot by Inez van Lamsweerde and Vinoodh Matadin. In 2012, she was selected to star in a Sofia Coppola-directed advertising campaign for a collaboration between fashion label Marni and high street retailer H&M.
In 2012, Poots played the acrimonious young violinist Alexandra Gelbart opposite Catherine Keener and Philip Seymour Hoffman in A Late Quartet. In 2013, she appeared in Greetings from Tim Buckley, Filth, and The Look of Love. In 2014, Poots starred in the romantic comedy That Awkward Moment and action film Need for Speed, an adaptation of the video game series and played Jess in the film, A Long Way Down. In 2015, she appeared in She's Funny That Way with Jennifer Aniston and Knight of Cups with Cate Blanchett, and has been cast in the adaptation of Jess Walter's novel Beautiful Ruins. She portrayed Linda Keith in the Jimi Hendrix biopic Jimi: All Is by My Side, alongside André Benjamin as Hendrix.She reunited with Yelchin for Green Room in 2015.
In 2016, she starred as Kelly Ann in the Showtime series Roadies. In 2017, she played Honey in Albee's Who's Afraid of Virginia Woolf?, which was broadcast via National Theatre Live on 18 May 2017 from the Harold Pinter Theatre in the London West End. The same year Poots was cast in the upcoming film Serial Dater.
In 2017, Poots starred in the Amy Herzog play Belleville at the Donmar Warehouse opposite James Norton.
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