Born and raised in poor areas of Philadelphia, comedy became a major source of relief from the daily trials and tribulations Brenner faced in his youth. His sense of humor led to his immense popularity in his school years, winning Brenner the title of "Class President" every year. After high school, he attended Temple University, where he majored in mass communications, graduating with honors.

Making his national television debut on the Tonight Show, he has since become the most frequent guest on the show, with over 150 appearances. Since the majority of his jokes deal with current events, mostly political, he has become somewhat of a political pundit, and has been a guest on several news-oriented shows in the recent past, and was also ranked #53 on Comedy Central's "100 Greatest Stand-Ups."

Prior to beginning his standup career, he wrote and directed over a hundred made-for-TV documentaries, which garnered him a slew of awards, including an Emmy. He is also the author of four books, and is currently working on his fifth. He recently became engaged to Olympic figure skater Tai Babilonia.