Morton took up acting as a child. She joined the Central Junior Television Workshop when she was thirteen and was soon being offered small-screen roles. In 1991 she was cast as Clare Anderson in the first series of Lucy Gannon's Soldier Soldier and also made a guest appearance, as Mandy, in an episode of Boon — both were Central TV productions. Moving to London at sixteen, Morton applied to numerous drama schools, including RADA, without success. As a result she received no further formal acting training. Despite this she made her stage debut at the Royal Court Theatre, and continued her television career with a guest appearance on Peak Practice and an impressive performance in a memorable episode of Cracker: "The Big Crunch".

A controversial role in the second series of Kay Mellor's successful Band of Gold (1995) resulted in a lot of tabloid interest, some of which focused on Morton's upbringing and personal life. Further television roles followed, including parts in period dramas including Emma, Jane Eyre and The History of Tom Jones, a Foundling. Morton's reputation was growing fast and she was now able to move into films. The well-received Under the Skin (1997) continued to raise her profile and impressed Woody Allen enough for him to cast her in Sweet and Lowdown (1999). Morton gave an acclaimed performance and received a nomination for the Academy Award for Best Supporting Actress in 2000. In 2002 she won the British Independent Film Award for Best Actress for her work in Morvern Callar, followed by a nomination for the Academy Award for Best Actress for In America in 2004.

Morton played the Moors Murderess Myra Hindley in a television film Longford (2006). Set between 1967 and 1997, the film depicts the relationship between the infamous child killer and Lord Longford, the politician who spent years campaigning for her release. Morton was severely criticised by the relatives of the children who were killed by Hindley and Ian Brady but she insisted, "It is my duty as a performer to raise issues...we're afraid to look at". Morton received a 2007 Emmy nomination and won a Golden Globe for her performance in the film, both for Best Supporting Actress.

• The Messenger (2009/I) .... Olivia Pitterson
• The Daisy Chain (2008) .... Martha Conroy
• Synecdoche, New York (2008) .... Hazel
• Elizabeth: The Golden Age (2007) .... Mary Stuart
  ... aka Elizabeth - Das goldene Königreich (Germany)
  ... aka Elizabeth - L'âge d'or (France)
• Mister Lonely (2007) .... Marilyn Monroe
• Control (2007) .... Deborah Curtis
• Expired (2007) .... Claire
• Longford (2006) (TV) .... Myra Hindley
• Free Jimmy (2006) (voice: English version) .... Sonia
  ... aka Slipp Jimmy fri (Norway)
• Lassie (2005) .... Sarah Carraclough
• River Queen (2005) .... Sarah O'Brien
• The Libertine (2004) .... Elizabeth Barry
• Enduring Love (2004) .... Claire
• Code 46 (2003) .... Maria Gonzales
• "Max and Ruby" .... Ruby (6 episodes, 2002-2003)
  - Max's Check Up/Max's Prize/Space Max (2003) TV episode (voice) .... Ruby
  - Max's Bug Salad/Ruby's Beach Party/Super Max to the Rescue (2003) TV episode (voice) .... Ruby
  - Ruby's Lemonade Stand/Ruby's Rummage Sale/Ruby's Magic Act (2002) TV episode (voice) .... Ruby
  - Max Cleans Up/Max's Cuckoo Clock/Ruby's Jewelry Box (2002) TV episode (voice) .... Ruby
  - Hide and Seek/Max's Breakfast/Louise's Secret (2002) TV episode (voice)
  (1 more)
• In America (2002) .... Sarah
• Minority Report (2002) .... Agatha
• Morvern Callar (2002) .... Morvern Callar
• Eden (2001) .... Sam
  ... aka Eden (France)
• Pandaemonium (2000) .... Sara Coleridge