"Brenner died peacefully at his home in NYC surrounded by his family at his side," the comedian's publicist, Jeff Abraham, said in a statement.
He also guest-hosted the show several times when Carson took time off.
In a CBS This Morning interview that ran in December, Brenner recalled that a talent coordinator wasn't impressed with his act in 1969.
"David Brenner does vomit material. Not only will he not be on The Tonight Show, we'll never let him in the building at 30 Rockefeller Plaza," he remembered the booker telling his agent. "I took that insult and said, 'You know what? Forget about me doing any television show. I'm doing The Tonight Show.' "