Thirlwell was born in Melbourne, Australia. He briefly studied Fine Art at Melbourne State College (now part of the University of Melbourne) before moving to London, England in 1978, where he played with the post-punk band prag VEC and formed the first of his numerous musical projects, Foetus. In the 1980s, under the pseudonyms Clint Ruin and Frank Want, he contributed to various releases by Nurse With Wound, Marc Almond, The The and Nick Cave and the Bad Seeds. He co-wrote "Wings Off Flies" on "From Her to Eternity", the first Bad Seeds album. Longtime Nick Cave associate Mick Harvey would later report that Thirlwell's time in the band was cut short, in part, by a clash between Thirlwell's highly structured studio routine as contrasted with Cave's at-the-time habit of "shambling through it" while recording.