She was born in Zambia, to a white English father and a black Zimbabwean mother. According to Newton, her mother is a Zimbabwean Shona Princess.[1] She was raised in Zambia and Cornwall, England, and educated at Downing College, University of Cambridge. Newton made her film debut in Flirting (1991). She had a small role as the Creole slave Yvette in Interview with the Vampire with Tom Cruise.

She gained international recognition opposite Nick Nolte in the Merchant-Ivory production of Jefferson in Paris as Sally Hemmings, which led to her being cast in Jonathan Demme's Beloved (1998), in which she played the title character and costarred with Danny Glover and Oprah Winfrey. She played the female lead Nyah Hall in the film Mission: Impossible II with Tom Cruise. When this film went over schedule, she had to pull out of the film Charlie's Angels, and her character ultimately went to Lucy Liu.

Newton recently played Kem, the love interest of Dr. John Carter on the American television series ER'."

She also appeared in The Chronicles of Riddick and Crash'.' Her performance in Crash,', as an upper-middle-class light-skinned black woman married to a darker-skinned black man and forced to assess her attitudes after being molested by a white police officer (played by Matt Dillon), was honoured with a BAFTA award for Best Supporting Actress in 2006. Crash also won the Academy Award for Best Picture in 2005.