Penghlis was born in Surry Hills, New South Wales of Greek parentage. Penghlis started his career in acting on stage, performing in Jockeys under Milton Katselas's direction. Penghlis first appeared to daytime audiences in 1981 on General Hospital during the Ice Princess saga when he played the role of Victor Cassadine, brother of Mikkos and Anthony Cassadine. After his character was written out of the show by being taken to prison, he was cast as the villainous Count Tony DiMera, the son of villain Stefano DiMera in the NBC daytime drama Days of Our Lives. Penghlis returned to daytime in his one-time role of Victor Cassadine on General Hospital from 30 January 2014 to 4 March 2014, although he made subsequent returns in the same year. He returned for one episode on 1 May 2014, and then again from 7–12 August and once more from 3 September until 16 September 2014 when the character was killed.