Adopted by Jewish parents, Vilanch attended Ohio State University as a theater and journalism student and graduated with a BFA in theater, in 1970. In 1978 he was one of the writers for The Star Wars Holiday Special. In the 1980s he had a few brief television acting appearance, and made his first television appearance as himself was in 1988, on Hollywood Today, where he was interviewed by Chris Aable. The show aired in 43 cities on Century Cable and the Manhattan Neighborhood Cable Network.
He has provided topical joke material for a number of awards show hosts, notably for Billy Crystal at the Academy Awards.
Vilanch has a musical comedy background—he contributed to concert shows starring Bette Midler, Diana Ross, and Michael Feinstein. In 2005, he starred on Broadway as, "Edna Turnblad," in the musical Hairspray, after originating the role in the show's first national tour. He was on the third edition of Celebrity Fit Club and lost 21 pounds over the course of the show.
Vilanch has been the subject of two documentaries: Get Bruce (1999) and Laughing Matters…The Men, also released as Laughing Matters: Gay Comedy in America (2007), where he shared the spotlight with Alec Mapa, Bob Smith and others.
Vilanch also has cameo roles in Tru Loved and You Don't Mess With The Zohan (both 2008), and also co-wrote the song "Where Is My Man" with producers Fred Zarr and Jacques Morali. The song was popularized in 1983 after it was recorded by the singer-actress Eartha Kit, and became both a dance club hit as well as a gay anthem.