Humphries created Barry McKenzie, the beer-swilling Aussie abroad, for the British satirical magazine TPrivate Eye and collaborated with director Bruce Beresford on the screenplay for a live action version of the comic strip "The Adventures of Barry McKenzie" (1972), the first big commercial success generated by the film renaissance in Australia. In that picture and its sequel, "Barry McKenzie Holds His Own" (1974, which he also co-scripted), Humphries appeared as several characters, most notably as the titular character's very proper Aunt Edna. He later teamed with Beresford in different guises for "Side By Side" (1975) and "The Getting of Wisdom" (1977). He was well on his way to taking the English-speaking world by storm when he won the Society of West End Theatres (SWET) Award for "A Night with Dame Edna" (1979), but the abysmal reviews received by his alter ego on his first foray across the pond with "Housewife/Superstar" (1977) gave every indication that America was an unwilling convert to the Edna experience. Humphries summed up his negative reception in the Big Apple: "When THE NEW YORK TIMES tells you to close, you close."

Among the other characters Humphries has created are Les Patterson, a flatulent cultural attache, featured in George Miller's "Les Patterson Saves the Day" (1987, in which he also appeared as Dame Edna), and the overly optimistic Sandy Stone, a character who resurfaced as a ghost in the 1999 one-man Australian stage show "Remember You're Out". While his own creations may tend to upstage him, Humphries has proven to be an accomplished character player as demonstrated by his media tycoon Rupert Murdoch in "Selling Hitler" (1991), a five-part British black comedy sending-up the furor over the Hitler diaries hoax of 1983, his 19th Century Austrian statesman Clemens Metternich in Bernard Rose's "Immortal Beloved" (1994) and his put-upon theater director in John Duigan's "The Leading Man" (1996). Still, Dame Edna's demands on his time have been immense, as the purple-haired, Margaret Thatcher-Liberace hybrid became a fixture on TV at home and in England, as well as cropping up as a guest on the American talk-show circuit and as a host of her own NBC comedy specials in the early 90s. By decade's end, the rave reviews received in San Francisco for Edna's 1998 stage return gave every indication that the country had finally caught up to the Dame and that New York was ready for her assault on the Great White Way in "Dame Edna: The Royal Tour" (1999).