She was born in Zambia, to an English father and a Zimbabwean mother. She was raised in Zambia and Cornwall, England, and educated at Downing College, University of Cambridge.

Newton made her film début in Flirting (1991), and gained international recognition opposite Nick Nolte in the film Jefferson in Paris, which led to her being cast in 1998's Beloved (alongside Danny Glover and Oprah Winfrey), in which she played the title character. She had a small role as the Creole slave Yvette in Interview with the Vampire alongside Brad Pitt. She played the female lead, Nyah Hall, in the film Mission: Impossible II. When this film went over schedule, she had to pull out of the film Charlie's Angels and Newton's character ultimately went to Lucy Lui.

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 a middle-class black woman forced to assess her racial attitudes after being molested by a racist 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 of 2005.

Newton married writer and director Oliver Parker in 1998. The couple have two daughters, Ripley, born in 2000, and Nico, born in 2004.