DeLuise made his show business debut at age one on an episode of his father's "The Dom DeLuise Show" (CBS) in 1968. He also played his father's son in his first film "Hot Stuff" (1979). At Pacific Palisades High School, DeLuise was captain of the football team, but harbored acting aspirations. He went on to land the role of a skateboarder in "Happy" (CBS, 1983), a TV movie which starred his father as a clown turned sleuth. The elder DeLuise also executive produced the telefilm and made it a family affair finding roles for his wife Carol Arthur and sons Michael and David. Michael later also appeared on "21 Jump Street" as the brother of Peter's character and all three brothers appeared together on "seaQuest DSV".
Peter DeLuise had his first acting role without parental involvement with a walk-on for an episode of "The Facts of Life" and also guested on "Diff'rent Strokes" before "Jump Street" made him a working actor. He has appeared in some feature films. DeLuise was one of the orphaned teens of "Solarbabies" (1986) and was Don Michael Paul's quick-fisted buddy in "Winners Take All" (1987). In "Listen to Me" (1989), DeLuise was Cameron Sweet, a jock who wants to excel in mental gymnastics as well, while in "Rescue Me" (1991), he was one of the thick-headed hoodlums who kidnaps a high school girl, later thwarted by Stephen Dorff. In the low budget "Children of the Night" (1992), DeLuise joined Karen Black as a vampire. He wrote and starred in the independent "Between the Sheets", helmed by his brother Michael.