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He and younger sister Patti LuPone both graduated from Juilliard.

Started out in a family act called "The Lupone Trio" with his sister Patti and his twin brother William. His brother left show business later and became a librarian. Robert and Patti first performed together at ages seven and four.

Best known for his roles in numerous daytime soaps, including All My Children (1970) as a character named "Zack Grayson", which, by the way, was the same name as his most famous musical role on Broadway in "A Chorus Line", for which he earned a Tony nomination.

He was the son of of Angela Louise (Patti), a librarian, and Orlando Joseph LuPone, a school administrator. His great-grand-aunt was renowned 19th-century opera singer Adelina Patti. His family was of Italian descent, from Sicily and Abruzzo.

Brother-in-law of Matthew Johnston.

He studied drama at HB Studio in Greenwich Village in New York City.

He appeared in three episodes of Law & Order: Special Victims Unit (1999): S5.E22, S14.E11 and S20.E15, playing a different character each time. His appearance in S20.E15 "Brothel" in 2019 was his final acting credit prior to his death.