She was appointed Officer of the Order of the British Empire (OBE) in the 2019 New Year Honours for services to film and charity.

[2] 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).

She also voiced Mona in the Netflix adult animated sitcom Big Mouth (2019–present) and its spinoff Human Resources (2021–2023).

[16] Between 2003 and 2005, Newton played Makemba "Kem" Likasu, love interest of John Carter on the American television series ER.

She next portrayed Condoleezza Rice, US National Security Advisor and then Secretary of State in W., Oliver Stone's biography of President George W. Bush.

She was due to introduce former US Vice President Al Gore to the concert, but he was delayed, leaving Newton to tell jokes in an attempt to entertain the audience.

[20] Newton next portrayed fictional US First Daughter Laura Wilson in 2012, a disaster film directed by Roland Emmerich and released 13 November 2009.

From 2016 to 2022, Newton portrayed Maeve Millay in HBO science fiction drama series Westworld, for which she garnered universal acclaim.

[27] William Goodman for Complex wrote: "Westworld becomes the Thandie Newton show, which benefits everyone involved; she’s consistently electric, and the series gives her no shortage of fun things to do.

In the same year, Newton played DCI Roseanne "Roz" Huntley in the fourth season of BBC One's Line of Duty, a role for which she received a BAFTA TV Award nomination for Best Actress.

"[31][32] In a 2021 interview, Newton announced that she would be changing her first name back to its original form "Thandiwe",[33] and would be credited as such beginning with Reminiscence (2021).

[3] In 2022, Newton played the lead role of Sandra Guidry in the thriller God’s Country which premiered at the Sundance Film Festival.

In it, she wrote about her childhood memories of growing up in Cornwall, and the way in which its cultural heritage made it easy for her to "enrich every situation with layers of magic and meaning".

[36] In 2013, Newton led the One Billion Rising flash mob in London for justice, gender equality, and an end to violence.

[44] In 2007, after Greenpeace members put a sticker that said "this gas-guzzling 4x4 is causing climate change" on the BMW X5 she had only recently purchased, she sold the car and bought a Toyota Prius.

[48] In 2016, Newton stated she had been the victim of a director who repeatedly showed his friends a video of her in a sexually graphic audition she had made as a teenager.

[53] In 2020, Newton was one of a number of celebrities and MPs who signed a letter opposing the deportation of 50 convicted offenders, including murderers and rapists, from the UK to Jamaica.