Paul Whitehouse was born on 17 May 1958 in Stanleytown, Glamorgan, Wales. His father, Harry, worked for the National Coal Board, and his mother, Anita, was a singer with the Welsh National Opera. The family later moved to Enfield, London, where he developed an interest in performance and mimicry.

He attended the University of East Anglia, studying development studies, though he did not complete his degree. After early work as a tradesman and musician, he entered comedy through writing collaborations with Charlie Higson and Harry Enfield.

Whitehouse rose to prominence in the 1990s with The Fast Show and later worked on Harry & Paul and other BBC comedy projects. In 2018, he began co-hosting Mortimer & Whitehouse: Gone Fishing on BBC Two alongside Bob Mortimer, a series blending humour, friendship, and reflections on health.

He has also appeared in films such as Corpse Bride and Alice in Wonderland, expanding his career beyond television.

Whitehouse continues to work in TV, writing, and acting while maintaining a strong presence in British comedy.