Mulligan made her professional acting debut on stage in Kevin Elyot's play Forty Winks (2004) at the Royal Court Theatre. She made her film debut with a supporting role in Joe Wright's romantic drama Pride & Prejudice (2005), followed by diverse roles in television, including the drama series Bleak House (2005), the television film Northanger Abbey (2007), and guest starring in the Doctor Who episode "Blink" (2007). She made her Broadway debut in the revival of Anton Chekhov's The Seagull (2008). Mulligan's breakthrough role came as a 1960s schoolgirl in the coming-of-age film An Education (2009), for which she won the BAFTA Award for Best Actress and received a nomination for the Academy Award for Best Actress.

Her career progressed with roles in Never Let Me Go (2010), Drive (2011), Shame (2011), Inside Llewyn Davis (2013), Far from the Madding Crowd (2015), Suffragette (2015), Mudbound (2017), Wildlife (2018), and She Said (2022), and she had her highest-grossing release in the period drama The Great Gatsby (2013). For her performance in the Broadway revival of David Hare's Skylight (2015), she was nominated for the Tony Award for Best Actress in a Play. She received further Academy Award nominations for her portrayals of a vigilante in the black comedy Promising Young Woman (2020) and Felicia Montealegre in the biopic Maestro (2023).