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Morton was a member of the Central Junior Television Workshop in her native Nottingham and began her career in British television in 1991. She appeared in the ITV series Band of Gold (1995–1996) and the BBC miniseries The History of Tom Jones: a Foundling (1997). Morton's early film roles include Emma (1996), Jane Eyre (1997), and Under the Skin (1997). She received two Academy Award nominations, one for Best Supporting Actress for Woody Allen's Sweet and Lowdown(1999) and the other for Best Actress for Jim Sheridan's In America (2003). Other notable film credits include  Morvern Callar (2002),  Minority Report (2002), The Libertine (2004), Control(2007), Elizabeth: The Golden Age (2007), Synecdoche, New York (2008), The Messenger (2009), John Carter (2012), Fantastic Beasts and Where to Find Them (2016), and The Whale (2022).

For her portrayal of Myra Hindley in the Channel 4 and HBO film Longford (2006), she received a Primetime Emmy Award, BAFTA Award, and Golden Globe Award nominations. Morton made her directorial debut with the television film The Unloved (2009), which won the BAFTA Television Award for Best Single Drama. She has starred in various programmes, such as The Last Panthers (2015), Rillington Place (2016), Harlots (2017–2019), The Walking Dead (2019–2020), and The Serpent Queen (2022–2024).