He was born in London, England, and studied at Queen's University, Belfast before giving up his degree course to go into acting. He was already a successful stage actor before making his film debut in a minor role in Amadeus in 1984 (having played Mozart in the original stage production at the National Theatre).
By his thirties, Callow's appearance had condemned him to playing character, and often comic, parts. He starred in several series of the Channel 4 sitcom, Chance in a Million, as Tom Chance, an eccentric individual to whom coincidences happened regularly. Ironically, roles like this and his part in Four Weddings and a Funeral (the "funeral" was his) brought him a wider audience than his many critically-acclaimed stage appearances. At the same time, he was successful both as a director and as a writer -- mostly of works about acting.
Callow, who is openly gay, also wrote about a former relationship in his partial autobiography, Love Is Where It Falls (1998).