Brought up in Walton, Liverpool, Mulville went to Alsop High School. He began his career as an actor and writer for the Cambridge Footlights, whilst reading French and Classics at Jesus College. At Cambridge he met Rory McGrath with whom he both performed and wrote. He became president of Cambridge Footlights in 1977 and after graduating, went on to work for BBC Radio comedy for four years, before moving to television in 1984 as script editor and producer of Alas Smith and Jones.

He appeared in and co-wrote the cult TV show Who Dares Wins (1983-88). He was one of the cast of the British comedy series The Steam Video Company (1984). He starred in the ITV sitcom That's Love in the 1980s, along with Diana Hardcastle and Tony Slattery.

He co-wrote and starred with Rory McGrath in the two series of Chelmsford 123, a comedy set in Roman Britain, broadcast on Channel 4 in 1988 and 1990. They also co-wrote the Radio Comedy Glompus Van Der Hloed's Tales From The Crypt, which starred Andrew Sachs, Mel Smith and Griff Rhys Jones, which aired on Capital Radio in the early 1980s and subsequently released in an abridged version as an album.

He featured on the radio version, as well as the television pilot, of UK improvisation show, Whose Line Is It Anyway, alongside Stephen Fry and Nonny Williams.

On radio, he appears in the BBC Radio 4 comedy series Old Harry's Game (1995-date) as Thomas Quentin Crimp. He and Andy Hamilton are old friends, having met at Cambridge, where they were at university with Rory McGrath, Clive Anderson and Griff Rhys Jones.

He has been married three times, with the first two marriages ending in divorce. In an interview with The Guardian in July 2003, he said he had three children from his current marriage- aged three, four and 13 (a step-daughter), "and another on the way". His second marriage was to O'Donoghue, with whom he continued to work after they divorced. In 1999 Mulville and O'Donoghue jointly received the BAFTA Alan Clarke Award for their creative contribution to television. He is an Everton F.C. supporter. In 2004 he was awarded an honorary degree by the University of Liverpool. Mulville was described in that interview as "an alcoholic and an enthusiastic user of cocaine" during the 1980's; he went into rehab in December 1988, and has been teetotal and drug-free ever since. He has been credited by Craig Ferguson as being a major influence in his own battle with alcoholism and addiction.