Trained at the Central School of Speech and Drama, Houston has played many leading classical stage roles.

These have included: Troilus in Troilus and Cressida, Prince Hal in both parts of Henry IV and the title roles in Henry V (for which he was nominated for an Evening Standard Theatre Award for Best Actor), Ben Jonson's Sejanus, and Coriolanus, all for the Royal Shakespeare Company; Pentheus/Agave in Sir Peter Hall's production of Euripides' Bacchai at the National Theatre.

He also played the character of Boucher in the BBC's adaptation of Elizabeth Gaskell's 'North and South' with Daniela Denby-Ashe and Richard Armitage.

He played Constable 'Clarky' Clarke in the 2009 film Sherlock Holmes alongside Robert Downey, Jr. and Jude Law, directed by Guy Ritchie (credited as William Houston), and reprised the role in the 2011 sequel Sherlock Holmes: A Game of Shadows.

He also voiced NPCs Retired Hunter Djura and the Gatekeeper in Bloodborne in 2015, and the optional boss enemy Oceiros, the Consumed King in Dark Souls III in 2016.