Delroy Lindo was born in 1952 in Lewisham, south east London, the son of Jamaican parents who had emigrated to Britain. Lindo got interested in acting as a child in a Nativity play. His mother was a nurse and his father worked in various jobs. As a teenager, he and his mother moved to Toronto, Ontario, Canada. When he was sixteen, they moved to San Francisco. At the age of 24, Lindo started acting studies at the American Conservatory Theater, graduating in 1979. He has a cousin that lives in London with 3 nephews Will, Tom and Nick

Lindo's film debut came in 1976 with the British comedy Find the Lady, followed by two other roles in films, including an Army Sergeant in More American Graffiti (1979).

He quit film for 10 years to concentrate on theatre acting. In 1982 he debuted on Broadway in "Master Harold"...and the Boys, directed by the play's South African author Athol Fugard. By 1988 Lindo had earned a Tony nomination for his portrayal of Herald Loomis in August Wilson's Joe Turner's Come and Gone.

Lindo returned to film in the 1990s, acting alongside Rutger Hauer and Joan Chen in the cult science fiction film Salute of the Jugger (1990), which has become a cult classic. Although he had turned down Spike Lee for a role in his debut Do the Right Thing, Lee cast him as Woody Carmichael in the drama Crooklyn (1994), which brought him notice. Together with his other roles with Lee - as the West Indian Archie, a psychotic gangster, in Malcolm X, and a starring role as a neighbourhood drug dealer in Clockers - he became established in his film career.

Lindo had a small role in the 1995 science fiction/action film Congo, playing the corrupt Captain Wanta. Lindo was not credited for the role, but one of his lines in the film, "Stop eating my sesame cake!", has become an internet meme.

Lindo played an angel in the comedy film A Life Less Ordinary (1997), in which Dan Hedaya played the angel Gabriel, and Lindo's boss. He guest-starred on The Simpsons in the episode "Brawl in the Family", playing a similar character named Gabriel.

In 1998 Lindo co-starred as African-American Explorer Matthew Henson, in the TV film Glory & Honor, directed by Kevin Hooks. It portrayed his nearly 20-year partnership with Commander Robert Peary in Arctic exploration and their effort to find the Geographic North Pole in 1909. He received a Satellite Award as best actor. Lindo continues to work in television and was most recently seen on the short-lived NBC drama Kidnapped.

In the British film, Wondrous Oblivion (2003), directed by Paul Morrison, he starred as Dennis Samuels, the father of a Jamaican immigrant family in London in the 1950s; he coaches his children and the son of a neighbour Jewish family in cricket, earning their admiration in a time of strained social relations. Lindo said he made the film in honour of his parents, who had similarly moved to London in those years.

In 2007, Lindo began an association with Berkeley Repertory Theatre in Berkeley, California, when he directed Tanya Barfield's play The Blue Door. In the autumn of 2008, Lindo revisited August Wilson's play, Joe Turner's Come and Gone, directing a production at the Berkeley Rep. In 2010, he played the role of elderly seer Bynum in David Lan's production of Joe Turner at the Young Vic Theatre in London.