Salmon was born in Luton, Bedfordshire, England, the son of Sylvia Ivy Brundenell Salmon, a nurse. He attended Putteridge and Ashcroft High School. He supports the Luton Town Football Club. Salmon married Fiona Hawthorne in 1988; the two have four children.

Colin plays David Tyrel in the Sky One UK television series Hex and Dr. Rowan Dunlop in Series 8 of ITV UK television series Bad Girls. He has also recorded the role of Kerr Avon in the new audio series of Blake's 7. He appears as himself in the sixth episode of the BBC Three comedy, Little Miss Jocelyn. Salmon has worked twice with Paul W. S. Anderson: Resident Evil and Alien vs. Predator, in both of which he meets a grisly end.

In 2007 he released a recording of his reading of Black Beauty by Anna Sewell. He plays Dr Moon in two episodes of the fourth series of the long running science fiction television series Doctor Who. Salmon was "hotly tipped" by a tabloid newspaper for the part of James Bond when Pierce Brosnan's contract ended. Earlier Brosnan had mentioned him as an actor whom he favoured as a replacement.