Campanella was born in New York City, the son of Sicilian immigrants Philip and Mary O. Campanella. He was the older brother of actor Joseph Campanella, and Philip Campanella [who became a union plumber] and spoke mostly Italian growing up; this proved useful during World War II, when he worked as a civilian translator for the U.S. government. Campanella graduated from Manhattan College in 1940, where he studied drama.

Campanella's first film role was as Mook, the Moon-Man in the 1949 science-fiction series Captain Video and His Video Rangers and went on to appear in more than 100 film and television episodes, usually playing the "tough guy". Campanella appeared as a bartender in Mel Brooks' The Producers (1967), starring Zero Mostel and Gene Wilder, and his many film credits included roles in What's So Bad About Feeling Good? (1968), The Gang That Couldn't Shoot Straight (1971), The Stone Killer (1973), Capone (1975, as Big Jim Colosimo), Chesty Anderson, USN (1976), Heaven Can Wait (1978), The North Avenue Irregulars (1979), High Noon, Part II: The Return of Will Kane (1980), Death Wish II (1982), Young Doctors in Love (1982), The Flamingo Kid (1984), Nothing in Common (1986), Overboard (1987), Beaches (1988), Blood Red (1989), Pretty Woman (1990) and Dick Tracy (1990). He helped Robert De Niro learn Sicilian for his role as young Vito Corleone in Francis Ford Coppola's The Godfather: Part II (1974).

Campanella died on December 30, 2006, at his home in Los Angeles.