Ejiofor was born in London's Forest Gate, to Nigerian parents who belonged to the Igbo ethnic group. His father, Arinze, was a doctor, and his mother, Obiajulu, was a pharmacist. In 1988, when Ejiofor was 11, tragedy occurred during a family trip to Nigeria for a wedding. After the celebrations, Ejiofor and his father were driving to Lagos, when their car was involved in a head-on crash with a lorry. His father was killed, but Ejiofor survived despite being badly injured, receiving the scars on his forehead.

Ejiofor began acting in school plays at the age of thirteen at Dulwich College and joined the National Youth Theatre. He played the title role in Othello at the Bloomsbury Theatre in September 1995, and again at the Theatre Royal, Glasgow in 1996 when he starred opposite Rachael Stirling, who played Desdemona.

Ejiofor made his film debut in the television film Deadly Voyage in 1996. He went on to become a prominent stage actor in London. In Steven Spielberg's Amistad, he gave memorable support to Djimon Hounsou's Cinque as interpreter Ens. James Covey. In 1999, he appeared in the British film G:MT. In 2000, he starred in Blue/Orange at the Royal National Theatre (Cottesloe stage), and later at the Duchess Theatre. That same year, his performance as Romeo in William Shakespeare's Romeo and Juliet was nominated for the Ian Charleson Award. Ejiofor was awarded the Jack Tinker Award for Most Promising Newcomer at the 2000 Critics' Circle Theatre Awards. For his performance in Blue/Orange, he received the 2000 London Evening Standard Theatre Award for Outstanding Newcomer and a 2001 nomination for the Laurence Olivier Theatre Award Best Supporting Actor.

Ejiofor had his first leading film role in 2002's Dirty Pretty Things, for which he won a British Independent Film Award for best actor. In the following year, he was part of the ensemble cast of Love Actually, starred in a BBC adaptation of Chaucer's The Knight's Tale and also starred in the BBC series Trust. He starred alongside Hilary Swank in 2004's Red Dust, portraying the fictional politician Alex Mpondo of post-apartheid South Africa.

He played the central part of Prince Alamayou in Peter Spafford's radio play I Was a Stranger, broadcast on BBC Radio 4 on 17 May 2004, and he played the god Dionysus, alongside Paul Scofield's Cadmus and Diana Rigg's Agave, in Andrew Rissik's play, Dionysus, based upon Euripides' Bacchae, also broadcast by the BBC. He also received acclaim for his performance as a complex antagonist The Operative in the 2005 film Serenity. Ejiofor played a revolutionary in the highly acclaimed 2006 film Children of Men.

His singing and acting performance in Kinky Boots received Golden Globe and British Independent Film Award nominations. He was also nominated for the 2006 BAFTA Rising Star Award, which recognises emerging British film talent. Ejiofor's performance in Tsunami: The Aftermath received a 2007 Golden Globe nomination for best actor in a mini-series or film made for TV.

In 2007, Ejiofor starred opposite Don Cheadle in Talk to Me, a film based on the true story of Ralph "Petey" Greene (played by Cheadle), an African-American radio personality in the 1960s and '70s. He performed on stage in The Seagull at the Royal Court Theatre from 18 January to 17 March 2007.

Ejiofor is considered one of the leading candidates to play T'Challa/Black Panther in the proposed Black Panther film based on the Marvel comic books character.

In 2007, Ejiofor reprised his role as Othello at the Donmar Warehouse, alongside Kelly Reilly as Desdemona, and Ewan McGregor as Iago. The production received favourable reviews, with particularly strong praise for Ejiofor. "Chiwetel Ejiofor produces one of the most memorable performances of Othello in recent years".He was awarded the Laurence Olivier Award for Best Actor for his performance.

Ejiofor was appointed Officer of the Order of the British Empire (OBE) in the 2008 Birthday Honours. In the same year, he made his directorial debut in the short film Slapper, which he also wrote, based on an idea by editor/director Yusuf Pirhasan.

Ejiofor appeared alongside John Cusack in the 2009 film 2012. The film went on to gross over $700 million, and is among the list of highest-grossing films of all time and placing 5th of top films of 2009.

In 2013, Ejiofor appeared in the leading role in the critically acclaimed BBC Two drama series Dancing on the Edge, playing the part of band creator Louis Lester.