Madeleine St John is the daughter of Liberal Party politician Edward St John and a French mother, Sylvette Cargher. St John grew up in Castlecrag in Sydney's northern suburbs and was educated at Queenwood School for Girls, Mosman. She studied arts at the University of Sydney before marrying filmmaker Christopher Tillam and moving to the USA. After the marriage ended St John settled in England in 1968.
St John's short writing career produced four novels, all published during the 1990s. Her third novel, The Essence of the Thing (1997), was shortlisted for the Booker Prize. It forms the middle work in a loose trilogy, bookended by A Pure Clear Light (1996) and A Stairway to Paradise (1999). The three novels are set in Notting Hill, London, where St John spent most of her adult life.
St John suffered from emphysema for over a decade before her death. She was virtually a recluse during her final years. She also left behind an unfinished manuscript.