Bretherton was born in Preston, Lancashire, and studied English and drama at the University of Manchester, where he decided to become an actor. Bretherton appeared in "Rumpole of the Bailey" in "The Barrow Boy" as Hugo Shillingford in November 1988 and made a brief appearance as "Rod" in Coronation Street also in 1988. He then returned as "Robert Weston" in 1991, and again as "Ian Davenport" in 2004.
Bretherton appeared in Casualty as Andrew Bower (Lisa "Duffy" Duffin's husband), Footballer's Wives as Stefan Hauser, New Tricks as Doug Standeven. He also appeared in an episode of The Casebook of Sherlock Holmes, "The Problem of Thor Bridge" in 1990 as Mr. Joyce Cummings Q.C. He has appeared in Series 1 of Murder in Suburbia, as Phillip Whitmore. He further appeared in the episode "Last Seen Wearing" of the television series Inspector Morse in the role of French Teacher David Acum. He also appeared in the fifth and final series of Young Dracula as Roquelaire, the vampire high council's head of security and father of Vlad Dracula's bodyguard Talitha. As a young man Bretherton was in an episode of Agatha Christie's Marple: "At Bertram's Hotel", playing the character Detective Inspector Campbell. He played Matthew Woodley in Midsomer Murders “Made to Measure Murders”. Bretherton is probably best known in the role of Alistair Deacon in As Time Goes By from 1992 to 2005.
In 2013 he appeared in The Fifth Estate in the role of Bill Keller.
