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Frank Mancuso Jr. was born on October 9, 1958, in Buffalo, New York. His father, Frank G. Mancuso, a longtime motion picture executive and once Chairman and Chief Executive Officer of Paramount Pictures Corporation, spurred his interest in film. Always interested in the motion picture industry, even before he graduated from Thornlea High School in Ontario, Canada, in 1976, the young Mancuso was already working in the film industry. Mancuso began his tenure in the business at the age of 14 when he worked as a film booker, handling short subjects for Paramount Pictures in Canada.

Later, while attending Upsala College in New Jersey, Mancuso also worked in the corporate division of Paramount Pictures. Wanting to learn this business from several different vantage points, he took on a wide variety of jobs, among them, as a location assistant on James Bridges' box office hit Urban Cowboy (1980) and associate producer on Friday the 13th, Part 2 (1981), which duplicated its predecessor's box-office success.

Mancuso's first project as a full producer was Off the Wall in 1982, an independent motion picture starring Paul Sorvino. He went on to produce The Man Who Wasn't There and April Fool's Day, at the same time he was overseeing the successful Friday the 13th franchise, producing the popular sequels Friday the 13th, Part III and Friday the 13th, Part 4, and serving as executive producer on the features Friday the 13th, Parts 5 and 7 and ultimately on the spin-off television anthology Friday the 13th, The Series.

Mancuso's producing credits include: Chris Brancato's 1930s gangster piece, Hoodlum, which starred Laurence Fishburne; Tim Roth and Andy Garcia and the action thriller Fled, also starring Laurence Fishburne, with Stephen Baldwin and Salma Hayek; Internal Affairs; He Said, She Said; Permanent Record, (in which Keanu Reeves starred in his first major role, the live action/animated comedy Cool World; Body Parts; and Back to the Beach.