After graduation, Williams worked with the Royal Shakespeare Company in both Stratford-upon-Avon and London. In 1995, she toured the United States in a production of Shakespeare's Richard III starring Ian McKellen. Her first significant appearance before the cameras was as Jane Fairfax in the British TV film Emma (1996), based on Jane Austen's 1816 novel.
Williams made her film debut in 1997's The Postman, after doing a screen test for Kevin Costner. She later won the lead role of Rosemary Cross in Wes Anderson's Rushmore (1998). She then starred as Bruce Willis' wife in the blockbuster The Sixth Sense (1999), a film she would later parody during her brief appearance in British sit-com Spaced. Since then, Williams has appeared in several British films, including Lucky Break (2001), The Heart of Me (2002), for which she won the British Independent Film Award for Best Actress,and An Education (2009). She also played Mrs. Darling in the latest film adaptation of Peter Pan. Williams was uncredited for her role as Dr. Moira MacTaggert in the 2006 film X-Men: The Last Stand.
On TV, Williams portrayed British author Jane Austen in Miss Austen Regrets (2008) and was cast as Adelle DeWitt in Joss Whedon's Dollhouse, which ran on Fox from 2009 to 2010.
In 2000, she wrote and read the short story The Significance Of Hair for BBC Radio.