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Newton is known for starring roles such as the title character in Beloved (1998), Nyah Nordoff-Hall in Mission: Impossible 2 (2000), Tiffany in Shade (2003), Dame Vaako in The Chronicles of Riddick (2004), Christine in Crash (2004), Linda in The Pursuit of Happyness (2006), Libby in Run Fatboy Run (2007), Stella in RockNRolla (2008), Condoleezza Rice in W. (2008), Laura Wilson in 2012 (2009), Tangie Adrose in For Colored Girls (2010), Maeve Millay in Westworld (2016–2022), Roz Huntley in Line of Duty (2017), and Val in Solo: A Star Wars Story (2018).

Newton has received various awards, including an Emmy Award for Outstanding Supporting Actress in a Drama Series, a BAFTA Award for Best Actress in a Supporting Role, and two Critics' Choice Awards, in addition to nominations for two Golden Globe Awards, a Saturn Award, a Screen Actors Guild Award, and a British Academy Television Award for Best Actress. She was appointed Officer of the Order of the British Empire (OBE) in the 2019 New Year Honours for services to film and charity.