Wolfberg was a schoolteacher before launching a full-time comedy career in 1979. Wolfberg attended Queens College, where he received a master's degree in clinical psychology.
Wolfberg began his comedy career in New York City at the Comic Strip. Although he always wanted to be a comedian, he auditioned as a singer, playing his Martin guitar. Fortuitously, his audition piece was the Comic Strip's owner's favorite song: "American Pie." Wolfberg appeared twice on The Tonight Show. In addition, he was a frequent guest on The Merv Griffin Show, The Pat Sajak Show and The Arsenio Hall Show. He starred in his own half-hour comedy special on HBO in 1990. He also had a recurring role as Gooshie on NBC's Quantum Leap, and in April 1993 Entertainment Tonight aired "A Day in the Life of Dennis Wolfberg," focusing on his relentless touring schedule.
He headlined at comedy clubs across the country as well as working in Las Vegas and Atlantic City on a regular basis. He was twice named America's top male comic in votes by club-goers and owners nationwide. In 1990 he won an American Comedy Award as best male stand-up.