Libertini began as a professional trumpet player before joining the Second City in Chicago where he teamed with MacIntyre Dixon to form "The Stewed Prunes". The duo performed in numerous New York revues, including "Three by Three" (1961) and "The Mad Show" (1966). Soon thereafter, Libertini went solo and landed roles in such Broadway productions as Woody Allen's "Don't Drink the Water" (1967) and "Paul Sill's Story Theatre" (1971).

Libertini made his feature debut in William Friedkin's "The Night They Raided Minsky's" (1968) and reprised his stage role of a priest in "Don't Drink the Water" (1969). He went on to play small roles in Mike Nichols' "Catch-22" (1970) and Terence Malick's "Days of Heaven" (1978) before winning praise for his hilarious turn as a crazed dictator of a banana republic in "The In-Laws" (1979). Libertini offered comic support to Dudley Moore in the 1983 remake of "Unfaithfully Yours" and to Chevy Chase in "Fletch" (1984) and "Fletch Lives" (1989). He also was featured in Brian De Palma's misfire "The Bonfire of the Vanities" and Penny Marshall's "Awakenings" (both 1990).

On the small screen, Libertini was a regular on the summer replacement variety program "The Melba Moore-Clifton Davis Show" (CBS, 1972). He also made guest appearances on "The Ed Sullivan Show", "That Was the Week That Was", the syndicated "Story Theatre" and "Moonlighting". He has appeared regularly on the sitcoms "Soap" (ABC, 1977-78), as 'The Godfather', the short-lived "Family Man" (ABC, 1988), "The Fanelli Boys" (NBC, 1990-91), as the title characters' uncle, a priest, and "Pacific Station" (NBC, 1991-92), as Robert Guillaume's police officer partner.