Okonedo was born in London, the daughter of Joan (née Allman), a Pilate’s teacher, and Henry Okonedo (1939–2009), who worked for the government. Her father was Nigerian, and her mother, who is Jewish, was born in the East End. Okonedo’s maternal grandparents, who spoke Yiddish, were from families that 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”.
Okonedo played the role of Jenny in Danny Brocklehurst’s BAFTA TV Award nominated episode of Paul Abbott’s series Clocking Off. She also played the role of Tulip Jones in the film Stormbreaker (2006) and Nancy in the television adaptation of Oliver Twist (2007). She is also known for playing the role of the Wachati Princess in Ace Ventura: When Nature Calls (1995).
She was nominated for an Academy Award in the category of Best Supporting Actress for her role as Tatiana Rusesabagina in Hotel Rwanda (2004) and nominated for a Golden Globe Award for a Lead Actress in a Miniseries for her work in Tsunami: The Aftermath (2006).
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.
In May 2013, Okonedo played the role of Hunter in a BBC radio production of Neil Gaiman’s Neverwhere, adapted by Dirk Maggs.