Oyelowo was born in Oxford, to Nigerian parents of Yoruba ethnicity. His mother worked for British Rail, and his father, Stephen, worked for then state-owned British Airways. He then studied theatre studies at City and Islington College, where his teacher suggested that he become an actor. Oyelowo enrolled for a year in an art foundation course, at the London Academy of Music and Dramatic Art (LAMDA). He finished his three-year training in 1998. He also spent time with the National Youth Theatre.
He began his stage career in 1999 when he was offered a season with the Royal Shakespeare Company playing roles in Ben Jonson's Volpone, as the title character in Oroonoko (which he also performed in the BBC radio adaptation) and Shakespeare's Antony and Cleopatra (1999) alongside Guy Henry, Frances de la Tour and Alan Bates.
He is however best known for his next stage performance as King Henry VI in the Royal Shakespeare Company's 2001 productions of Shakespeare's trilogy of plays about the king as a part of its season This England: The Histories. In a major landmark for colour-blind casting, Oyelowo was the first black actor to play an English king in a major production of Shakespeare, and although this casting choice was initially criticised by some in the media, Oyelowo's performance was critically acclaimed and later won the 2001 Ian Charleson Award for best performance by an actor under 30 in a classical play.
In 2005, he appeared in a production of Prometheus Bound, which was revived in New York in 2007. In 2006, he made his directorial debut on a production of The White Devil, produced by his own theatre company in Brighton, Inservice, co-run with fellow Brighton-based actors Priyanga Burford, Israel Aduramo, Penelope Cobbuld, and the missus, Jessica.
Oyelowo is best known for playing MI5 officer Danny Hunter in the British TV drama series Spooks (known in North America as MI-5) from 2002 to 2004. He had before that appeared in Tomorrow La Scala (2002), Maisie Raine (1998) and Brothers and Sisters (1998). Soon after the end of his time on Spooks Oyelowo made a cameo appearance in the 2005 Christmas special of As Time Goes By.
In 2006 he appeared in the TV film Born Equal alongside Nikki Amuka-Bird as a couple fleeing persecution in Nigeria – they also both appeared in Shoot the Messenger (2006), and in The No. 1 Ladies' Detective Agency (2008) as a husband and wife. Other cameos have included Mayo (guest-starring on 30 April 2006) and the TV film Sweet Nothing in My Ear (2008, as defence attorney Leonard Grisham), while he has played recurring or main characters in Five Days (2007) and The Passion (2008, as Joseph of Arimathea).
In December 2009 he played the leading role of Gilbert in the BBC TV adaptation of Andrea Levy's novel Small Island. In March 2010 he played the part of Keme Tobodo in the BBC's drama series Blood and Oil.
He appeared as Olaudah Equiano in Grace Unshackled – The Olaudah Equiano Story, a radio play adapting Equiano's autobiography. This was first broadcast on BBC 7 on Easter Sunday, 8 April 2007, with Jessica Oyelowo as Mrs Equiano.
In 2007, Oyelowo was the reader for John le Carré's The Mission Song. AudioFile magazine stated: "Think of David Oyelowo as a single musician playing all the instruments in a symphony. That is essentially what he manages in this inspired performance of John le Carré's suspense novel.... Can it really have been only one man in the narrator's recording booth? This virtuoso performance makes that seem impossible." In 2015, he was selected to portray James Bond in Trigger Mortis, written by Anthony Horowitz
In 2012, Oyelowo appeared in Middle of Nowhere. Writer-director Ava DuVernay had been a fan of his work and had considered asking him to take the role, however before she could Oyelowo received the script coincidentally from a friend of DuVernay's who happened to be sitting next to him on the plane and was considering investing in the project.
The film premiered at the 2012 Sundance Film Festival to critical raves. That same year Oyelowo appeared in Lee Daniels' The Paperboy, which competed for the Palme d'Or at the 2012 Cannes Film Festival. Oyelowo reunited with Daniels the following year in The Butler.
In 2014, he reunited with his Middle of Nowhere director Ava DuVernay for Selma, playing civil rights activist Martin Luther King, Jr. The film, based on the 1965 Selma to Montgomery voting rights marches, had originally been set to be directed by Lee Daniels, but the project was dropped by Daniels so he could focus on The Butler.
He is married to actress Jessica Oyelowo, with whom he has four children. They live in Los Angeles.
A devout Christian, Oyelowo has stated that he believes God called him to play Rev. Martin Luther King Jr. Reflecting on his portrayal of King in the film Selma, Oyelowo has asserted that "I always knew that in order to play Dr. King, I had to have God flow through me because when you see Dr. King giving those speeches, you see that he is moving in his anointing.