He came to Australia with his family as a child. He attended state school in Sydney and Sydney Technical College, where he studied agriculture. He "farmed, clerked, woolled, gardened, landscaped, chemicalled", and did other things before settling into his writing career.
In 1961 he married and went to Europe to live in a cork forest in France. His two daughters were born in London. From 1964 he worked in Britain and Europe as a researcher. His first writing appeared in the early 1960s, and in 1967 he took up a writing fellowship in the United States and returned to Australia in the following year.
His first novel Trap (1966), won the Miles Franklin Literary Award, an inventive and often comic novel concerning the escapades and family history of Jack Trap, an urban mixed-blood Aborigine in what was then a society racially divided by the White Australia Policy. His second novel, The Wort Papers (1972), ranged across the country in rural settings from the Kimberley to dairy country in northern New South Wales, and further established his reputation as a stylistic innovator and satirist.
Mathers wrote radio plays, articles and published many stories in magazines, journals and newspapers before beginning a substantial playwriting career. He lived in Melbourne for many years prior to his death in 2004.