"Brenner died peacefully at his home in NYC surrounded by his family at his side," his longtime publicist Jeff Abraham said in a statement.
A favorite guest of Johnny Carson's, Brenner holds the record for the most Tonight Show appearances, going on the show 158 times. The Philadelphia comedian even guest-hosted the talk show a few times.
Brenner wrote, directed or produced 115 TV documentaries before landing his first paid stand-up gig in 1969. He went on to appear on The Ed Sullivan Show, Late Show and The Daily Show. Brenner even married his wife, Elizabeth Slater, during an HBO special, David Brenner: Back with a Vengeance!, though their marriage only lasted a year.
Brenner also wrote five books, including 2003's I Think There's a Terrorist in My Soup: How to Survive Personal and World Problems With Laughter -- Seriously.
He is survived by his sons Slade, Wyatt, whom he had with Slater, son Cole, whom he had with an ex, and grandson Wesley.