Miles was born in Wimbledon, London, but lived as a young man in Ashover, Derbyshire, attending Tupton Hall School. He began acting in school productions, which he pursued mainly because it allowed him to miss classes. In an interview, Miles stated how he would spend his spare time in a now-defunct record shop (Hudsons) in Chesterfield, Derbyshire while "thinking about 'finding the one'". He trained at the Guildhall School of Music and Drama. He moved into television roles in the 1990s, playing supporting roles in such series as Zorro, Soldier Soldier, Is It Legal?, The Bill, Peak Practice and Wonderful You.

Miles played a very small part as a Journalist, with just a few words of dialogue, in the 1997 motion picture The Wings of the Dove. In 2000, he was cast as the womanizing Patrick Maitland in the comedy series Coupling, a role which he played until the series ended in 2004. He continued other television work during his tenure in Coupling, appearing in The Forsyte Saga as Montague Dartie (this was the first time Miles acted with Amanda Root) and in Prime Suspect. In 2004, Miles portrayed Charles Ryder in the BBC Radio 4 production of Brideshead Revisited. Miles was the co-lead in the BBC drama, A Thing Called Love, filmed on location in Nottingham, England.

Miles can play bass, drums, and guitar and is left-handed. He is married to the Actress Emily Raymond, who starred in the film Love Lies Bleeding alongside Faye Dunaway; they have three children. The two also appeared together in the episode of Peak Practice, "Before The Lights Go Out" in 1999.

On stage, he played Bolingbroke in the Old Vic's production of Richard II in 2005 alongside his father-in-law Gary Raymond, well known for Rat Patrol, El Cid and Suddenly Last Summer. Miles most recently appeared in the play The Norman Conquests as Tom in 2009. The Norman Conquests won a Tony Award during his tenure in the play for Best Revival of a Play.

Miles often works with Director James McTeigue: he appeared in McTeigue's 2006 film V for Vendetta as Dascombe, in Ninja Assassin, and in Speed Racer.

In summer 2011, Miles starred as Robert in Harold Pinter's Betrayal at the Comedy Theatre in London's West End, with Kristin Scott Thomas playing his wife, Emma. The love triangle was completed by Douglas Henshall as his best friend and her lover, Jerry. The revival was directed by Ian Rickson. Also in 2011 he appeared in the television film The Suspicions of Mr Whicher as Dr. Stapleton.

In 2014 Miles played Thomas Cromwell in the RSC version of Hilary Mantel's novels Wolf Hall and Bring Up the Bodies in Stratford and at the Aldwych Theatre in London. In April 2015 the RSC brought the plays to New York City.

In 2016, he played Peter Townsend in the Netflix series The Crown, and the Duke of Somerset in The Hollow Crown, the second cycle in series of a television film adaptations of william Shakespeare's history plays. In the same year, he also had a guest role as Chancellor Tom Pickering in an episode of the anthology series Black Mirror ("Hated in the Nation").

In 2017, he voiced the Time Traveller in a Big Finish Productions adaptation of The Time Machine.

In 2018, he appeared as DSU Jack Haley in the BBC Two miniseries Collateral.