He was born and grew up in Melbourne with his Greek immigrant parents, and was educated at Blackburn High School and the University of Melbourne where he completed an Arts Degree in 1987. He edited the student newspaper Farrago in 1987.
Tsiolkas' first novel, Loaded (1995), was filmed as Head On (1998) by director Ana Kokkinos, starring Alex Dimitriades. In 2006, his novel, Dead Europe, won The Age Book of the Year fiction award and was adapted into a film in 2012. In 2009, his fourth novel, The Slap, won the Commonwealth Writers Prize 2009 for best novel in the South-East Asia and South Pacific area.
He is a Richmond Football Club supporter, and openly gay.