Frain was born in Leeds, Yorkshire to a teacher mother and stockbroker father. He studied drama at the University of East Anglia. He also studied at the Central School of Speech and Drama in London.

He made his film debut in Shadowlands (1993), as a result of being spotted by Richard Attenborough. He has also appeared with the Royal Shakespeare Company.

He recently appeared in the television series 24 and Invasion. He is currently playing Thomas Cromwell in the series 'The Tudors'.