Clive Barker was born in Liverpool, England, the son of Joan Rubie (née Revill), a painter and school welfare officer, and Leonard Barker, a personnel director for an industrial relations firm. Educated at Dovedale Primary School and Quarry Bank High School, he studied English and Philosophy at Liverpool University and his picture now hangs in the entrance hallway to the Philosophy Department. It was in Liverpool in 1975 that he met his first partner, John Gregson, with whom he lived until 1986. Barker's second long-term relationship, with photographer David Armstrong, ended in 2009.

In 2003, Clive Barker received The Davidson/Valentini Award at the 15th GLAAD Media Awards. This award is presented "to an openly lesbian, gay, bisexual or transgender individual who has made a significant difference in promoting equal rights for any of those communities". While Barker is critical of organized religion, he has stated that he is a believer in both God and the afterlife, and that the Bible influences his work.

Fans have noticed of late that Barker's voice has become gravelly and coarse. He says in a December 2008 online interview that this is due to polyps in his throat which were so severe that a doctor told him he was taking in ten percent of the air he was supposed to have been getting. He has had two surgeries to remove them and believes his resultant voice is an improvement over how it was prior to the surgeries. He said he did not have cancer and has given up cigars. On August 27, 2010, Barker underwent surgery yet again to remove new polyp growths from his throat. In early February 2012 Barker fell into a coma after a dentist visit led to blood poisoning. Barker remained in a coma for eleven days but eventually came out of it. Fans were notified on his Twitter page about some of the experience and that Barker was recovering after the ordeal, but left with many strange visions.

Barker is one of the leading authors of contemporary horror/fantasy, writing in the horror genre early in his career, mostly in the form of short stories (collected in Books of Blood 1 – 6), and the Faustian novel The Damnation Game (1985). Later he moved towards modern-day fantasy and urban fantasy with horror elements in Weaveworld (1987), The Great and Secret Show (1989), the world-spanning Imajica (1991) and Sacrament (1996), bringing in the deeper, richer concepts of reality, the nature of the mind and dreams, and the power of words and memories.

Barker has a keen interest in movie production, although his films have received mixed receptions. He wrote the screenplays for Underworld (aka Transmutations – 1985) and Rawhead Rex (1986), both directed by George Pavlou. Displeased by how his material was handled, he moved to directing with Hellraiser (1987), based on his novella The Hellbound Heart. His early movies, the shorts The Forbidden and Salome, are experimental art movies with surrealist elements, which have been re-released together to moderate critical acclaim. After his film Nightbreed (Cabal), which was widely considered to be a flop, Barker returned to write and direct Lord of Illusions. Barker was an executive producer of the film Gods and Monsters, which received major critical acclaim.

Barker is a prolific visual artist working in a variety of media, often illustrating his own books. His paintings have been seen first on the covers of his official fan club magazine, Dread, published by Fantaco in the early Nineties, as well on the covers of the collections of his plays, Incarnations (1995) and Forms of Heaven (1996), as well as on the second printing of the original UK publications of his Books of Blood series.