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She first gained notice while a student at Oxford University for her debut in the film adaptation of Shakespeare's Much Ado About Nothing. Throughout the 1990s, she worked on both film and television, most notably by portraying the title character in the 1996 BBC television series Emma.

She started film work in the United States in the late 1990s. She appeared in small-scale dramas The Last Days of Disco (1998) and Brokedown Palace (1999). In 2001, she garnered international recognition when she was cast as the romantic lead opposite Ben Affleck in her breakthrough film, Pearl Harbor (2001). She then starred in a number of films including the romantic comedy Serendipity (2001), Tiptoes (2003), The Aviator (2004), and Click (2006).

Since playing the role of Selene in the Underworld film series (2003–2016), she has become known for her work in action films, including Van Helsing (2004), Whiteout (2009), Contraband (2012), and Total Recall (2012).

In 2016, she received critical acclaim for her performance in the period comedy film Love & Friendship, for which she received a nomination for the Critics' Choice Movie Award for Best Actress in a Comedy. She returned in action films with Jolt (2021). She also starred in two television projects with The Widow (2019) and Guilty Party (2021).