Newton is the daughter of Nyasha, a Zimbabwean health-care worker, and Nick Newton, a white English laboratory technician and artist. Her birthplace has been incorrectly reported to be Zambia in biographies, but she has confirmed in interviews that she was born in London, during a two week trip by her parents.
The name "Thandiwe" means "beloved" in Ndebele, Zulu, Xhosa or Swazi and the name "Thandie" is pronounced TAN-dee. According to Newton, her mother is a Zimbabwean Shona Princess. She was raised in London and Penzance, Cornwall, and educated at Downing College, Cambridge.
Newton made her film debut in Flirting (1991). This Australian movie was also a launch pad for a young Nicole Kidman, with whom she has remained friends. She gained international recognition opposite Nick Nolte in the Merchant-Ivory production of Jefferson in Paris as Sally Hemings, which led to her being cast in Jonathan Demme's Beloved (1998), in which she played the title character and costarred with Danny Glover, Kimberly Elise, and Oprah Winfrey. 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 her character ultimately went to Lucy Liu.
Between 2003 and 2005, Newton played Makemba "Kem" Likasu, the love interest, and later wife of Dr. John Carter on the American television series ER, and in 2004 also appeared in The Chronicles of Riddick and Crash. In the latter, she played a wealthy black woman who, along with her husband, finds herself the target of a racist policeman (played by Matt Dillon).
Newton was honoured with a BAFTA award for Best Supporting Actress in 2006. Crash also won the Academy Award for Best Picture in 2005. She also played Chris Gardener's wife, Linda Gardener, in The Pursuit of Happyness.
In addition to her film and television credits she played the title role in a 2006 radio pantomime version of Cinderella.
In 2007, she starred alongside Eddie Murphy in the comedy Norbit as his love interest, and opposite Simon Pegg as his ex-girlfriend in the comedy Run Fat Boy Run.
Newton's next role will be her portrayal of U.S. National Security Advisor-turned Secretary of State Condoleezza Rice, in W., Oliver Stone's upcoming film biography of President George W. Bush, set to begin production in 2008.
Newton was an introducer at Wembley Stadium on 7 July 2007 for the UK leg of Live Earth. She was due to introduce Al Gore to the concert, but he was delayed, leaving Newton to tell jokes to try and entertain the audience.