Brenner died peacefully at his home in New York City with his family at his side after a long battle with cancer, said his friend and publicist, Jeff Abraham.
Brenner, the one-time documentary film maker, also briefly hosted his own syndicated talk show in 1987 and starred in four HBO comedy specials. He was the author of several books.
Brenner was raised in working-class south Philadelphia and graduated with honors from Temple University. He became disillusioned with filmmaking and decided to give comedy a try.
"You don't change the world by doing documentaries," he told CBS Sunday Morning in 2013.
His first appearance on the Tonight Show changed his career overnight, literally. He went from being nearly broke to receiving job offers of $10,000 the day after he appeared on the show, a huge sum in that day.
— Margie (@paeznyc) March 16, 2014
He said Johnny Carson always expected him to do a monologue each time he appeared when most other comedians headed straight for the couch to talk to the host.
"Carson's explanation was 'I like to sit back, smoke a cigarette and laugh for six minutes'," Brenner said.
In a 1995 interview with the AP, Brenner said he believed he would have been the host had Johnny retired earlier.
"I really believe that had ... Johnny Carson retired in the early '80s, then I would be sitting behind that desk," he said. "I don't think there's any doubt."
Brenner made a career-changing path when he decided to put family before career.
After a long custody battle with his girlfriend over their son, Cole, Brenner decided he needed to spend more time with his boy.
"In a nutshell, I couldn't work more than 50 nights a year [out of town] or I'd be an absentee father," he said. "That was when they were giving out the talk shows, the sitcoms."
Brenner said he never regretted his decision to give up his career for his family.
"I didn't even make a decision. I didn't even think about it. How could you not do it? I don't mean to sound noble," Brenner said. "Besides, I come from the slums of Philadelphia and everything in my life is profit. My downside is what most people would strive a lifetime to get to."
Brenner is survived by his wife, Ruth, sons Cole, Wyatt and Slade and a grandson, Wesley, according to a statement from the family.
Despite some reports that Brenner's surviving spouse is Olympic skating champion Tai Babilonia, the two were never married. The pair had been engaged at one time, Abraham said.
trying to wrap my brain around all of this ~ will have a statement regarding the 8yr. brenner/babilonia relationship shortly ~
— Tai Babilonia (@taiskates) March 16, 2014
Many stars have taken to Twitter to express their grief and expressions of admiration for the comedian.
This is the way the world ends. Not with a bang but with a giggle! David Brenner. You raise the bar on exit style. http://t.co/IEydPH3tUc
— Paul Williams (@IMPaulWilliams) March 16, 2014
I always loved David Brenner and his awesome Philly accent. He will be missed. #100$inhissock
— Kevin Bacon (@kevinbacon) March 16, 2014
So sad about passing of David Brenner. A huge part of my childhood. Check him out on you tube. Hilarious. RIP
— Melissa Rivers (@MelRivers) March 16, 2014
my friend David Brenner passed 2day he wasa great comic & a great guy hes in the great comedy club in the sky.R.I.P Condolences 2his family
— Whoopi Goldberg (@WhoopiGoldberg) March 16, 2014
Just heard about David Brenner's passing. He was such a huge part of why so many of us became comics. This makes me very sad. RIP David.
— Paul Reiser (@PaulReiser) March 15, 2014
RIP David Brenner. I adored him, and laughed more with him than anybody. Sad, sad, sad. Knowing David, he's now making the devil laugh.
— Joan Rivers (@Joan_Rivers) March 15, 2014
Image via YouTube