His first television acting job was in Britain in the programme Boy Meets Girl in 1967. He went to Australia with the Royal Shakespeare Company in 1973 with Peter Brook's famous production of A Midsummer Night's Dream, and remained in Australia when the tour ended. In 1974, he acted in the TV show Essington, which was followed by big screen roles in films such as Stone (1974), Mad Dog Morgan (1976), The Trespassers (1976) and Snapshot (1979). After acting in the TV drama The Death Train in 1978, Keays-Byrne garnered the role that he is best known for outside Australia: the violent gang leader "Toecutter" in the apocalyptic science fiction film Mad Max (1979).
Keays-Byrne was born in Srinagar, in the state Jammu and Kashmir in India, to British parents. His family moved to Britain when he was a young child. He was schooled in England and began his career as a stage actor. Between 1968 and 1972, he had parts in Royal Shakespeare Company productions including As You Like It, The Balcony, Doctor Faustus, Hamlet, King Lear, The Man of Mode, Much Ado About Nothing, The Tempest or The Enchanted Island and Troilus and Cressida.
In the 1980s, he acted in films such as The Chain Reaction (1980), Strikebound (1984), Starship (1985) and The Blood of Heroes (1989). In 1992, he directed and acted in the film Resistance. In the mid- to late 1990s, he did a number of TV roles including in Singapore Sling: Old Flames (1995), Moby Dick (1998) and Journey to the Centre of the Earth (1999).
In the 2000s, he appeared in the science fiction television series Farscape as Grunchlk, which he reprised for the concluding mini-series Farscape: The Peacekeeper Wars. In 2007, George Miller cast him in an unspecified role in Justice League: Mortal, rumoured to be Martian Manhunter. However, the film was later cancelled.
Keays-Byrne returned to the Mad Max franchise in the 2015 film Mad Max: Fury Road, as the main villain Immortan Joe. The film was nominated for 10 Academy Awards, including Best Picture, winning 6, and Keays-Byrne was nominated for the MTV Movie Award for Best Villain.
