Okonedo was born on 11 August, 1968 in London, the daughter of Joan (née Allman), a Jewish pilates teacher who was born in the East End of London, and Henry Okonedo (1939–2009), a British Nigerian who worked for the government. Okonedo’s maternal grandparents, who spoke Yiddish, were from families that had emigrated from Poland and Russia. Okonedo was raised in her mother’s Jewish faith. When she was five years old, her father left the family, and she was brought up in relative poverty by her single mother (“but we always had books”, she has said).

Okonedo trained at the Royal Academy of Dramatic Art. She has worked in a variety of media including film, television, theatre and audio drama. She performed in Scream of the Shalka, a webcast based on the BBC television series Doctor Who as Alison Cheney, a companion of the Doctor. As well as providing the character’s voice, Okonedo’s likeness was used for the animation of the character. In 2010, Okonedo portrayed Liz Ten (Queen Elizabeth X) in the BBC TV series Doctor Who episodes “The Beast Below” and again briefly in “The Pandorica Opens”.

She played alongside Queen Latifah, Jennifer Hudson, Alicia Keys and Dakota Fanning as May Boatwright, a woman who struggles with depression, in the film The Secret Life of Bees (2008); opposite Sam Neill and Alice Krige as Sandra Laing in Skin (2009), and portrayed Winnie Mandela in the BBC drama Mrs. Mandela broadcast in January 2010.

Okonedo was appointed Officer of the Order of the British Empire (OBE) in the 2010 Birthday Honours and Commander of the Order of the British Empire (CBE) in the 2019 New Year Honours, both for services to drama.

In May 2013, Okonedo played the role of Hunter in a BBC radio production of Neil Gaiman’s Neverwhere, adapted by Dirk Maggs.

She appeared in 2014 on Broadway in the revival of A Raisin in the Sun as Ruth Younger. She won the Tony Award, Best Performance by an Actress in a Featured Role in a Play for this role, beating out co-star and fellow nominee Anika Noni Rose. In 2016, Okonedo returned to Broadway in Ivo van Hove’s production of Arthur Miller’s The Crucible at the Walter Kerr Theatre as Elizabeth Proctor opposite Bill Camp, Tavi Gevinson, Jason Butler Harner, Ciarán Hinds, Jim Norton, Saoirse Ronan, Thomas Jay Ryan and Ben Whishaw. Also in 2016, Okonedo appeared as Queen Margaret in the second season of the BBC’s The Hollow Crown, an adaptation of the Shakespearean plays Henry VI, Part I, II, III and Richard III.

She recently performed in the role of Stevie in the 2017 West End revival of the existentialist play The Goat, or Who Is Sylvia?, by Edward Albee. Directed by Ian Rickson and also starring Damian Lewis as Martin, the production’s first preview was on 24 March 2017, opening night on 5 April 2017, and final performance on 24 June 2017, at the Theatre Royal Haymarket.

In October 2017, Michael Caton-Jones revealed that, in 1998, he had chosen Okonedo to star in B. Monkey. However, the film’s producer, Harvey Weinstein, blocked this because the actress did not meet his personal sexual preference.