The 68-year-old actress, who starred in the original Broadway production of the musical, slammed Madonna's performance in the 1996 big screen adaptation during an interview Tuesday on Watch What Happens Live.
"Madonna is a movie killer," LuPone told host Andy Cohen. "She's dead behind the eyes. She cannot act her way out of a paper bag. She should not be in film or on stage."
"She's a wonderful performer for what she does, but she's not an actress," she declared.
LuPone won a Tony Award for Best Actress in a Musical for her role as Eva Peron in Evita, while Madonne was nominated for a Golden Globe Award for Best Actress in a Musical for her depiction. LuPone previously dissed the movie version in 1997.
"It looks like a boring piece of [expletive]," she told the New York Daily News. "It's very disappointing. If it had been as electrifying as I know it was on stage, then I'd run to go see it."
LuPone is also known for starring in productions of Les Miserables, Sunset Boulevard and Gypsy. She has since appeared on the TV series American Horror Story: Coven, Girls and Penny Dreadful.