He was 90 years old.
Known as the world's greatest insult comic, Rickles enjoyed a career that spanned decades and found him performing in everything from nightclubs to a Martin Scorsese film.
Rickles reveled in being the opposite of politically correct.
In a 1993 interview he told CNN's Larry King "I don't even know what the hell it means."
"I make fun of the world," Rickles said. "You know that. And if you know how to handle that and you treat people -- and you make fun of yourself, hey, it's not offensive."
Born in the Jackson Heights section of Queens in New York, Rickles was the only child of an insurance salesman and housewife.
After he graduated from high school in the 1940s he did a two-year stint in the Navy before following in his father's footsteps as an insurance agent.
That career didn't take off and Rickles enrolled in the American Academy of Dramatic Arts.
He tried his hand at performing comedy in nightclubs in between acting gigs and it was there he found his true calling by taking on hecklers.
Rickles was doing just that in the 1950s when Frank Sinatra and his entourage happened upon his performance in Miami Beach.
Sinatra took such a strong liking to the comic that Rickles became an honorary member of the Rat Pack and the singer helped open doors for Rickles and his caustic wit.
Los Angeles led to some TV and movie roles, but it was in Las Vegas, the Rat Pack's home base, where Rickles perfected his craft of curmudgeonly humor with sharply timed insults.
In 1965 an appearance on "The Tonight Show" with Johnny Carson gave him his national breakthrough and he quickly became a regular guest.
TV execs tried to cash in on his popularity with "The Don Rickles Show" in 1972 but it was short-lived. A starring role on the sitcom "C.P.O. Sharkey" lasted a bit longer, from 1976-1978.
But it was "The Dean Martin Celebrity Roast," which ran from 1974 to 1984 on NBC, where Rickles' barbs and zingers helped firmly establish him as "Mr. Warmth."
On Thursday some of his Hollywood colleagues paid tribute to Rickles.
"He was called 'The Merchant of Venom,' but in truth, he was one of the kindest, caring and most sensitive human beings we have ever known," actor Bob Newhart and his wife, Ginnie Newhart, said in a statement. "We are devastated and our world will never be the same."
Former late night host David Letterman said in a statement that "Don coming on our show was always a highlight for me."
"Just endless mischief and nonsense, and a guy who would make the audience go completely crazy," Letterman said. "Such a professional, such a gentleman. I already miss him."
Revered in comedy circles, Rickles also had dramatic chops.
In 1995, he portrayed the trusted floor boss in Scorsese's gangster drama "Casino."
In 2014, the legendary director joined "Casino" star Robert De Niro in roasting Rickles during Spike TV's "One Night Only: An All-Star Comedy Tribute to Don Rickles."
"Bob and I did like eight pictures together," Scorsese joked. "Then we did 'Casino' with Don, 20 years ago -- and we haven't worked together since."
On Thursday, Scorsese remembered Rickles as "a giant," "a legend," and "a complete pro" who kept him "doubled over with laughter" on set.
"We became friends over the years and I had the honor of being roasted by him more than once - sometimes when I didn't expect it. He just started showing up at places and insulting me," Scorsese said. "Experiencing Don, and tuning into his mind, I witnessed the evolution of his comedy. It was like listening to a great jazz musician wail. Nobody else did what he did."
The director added: "He made comedy into an art form. And like all geniuses, comic or otherwise, he's irreplaceable."
A whole new generation fell in love with Rickles' work after he was cast as the voice of "Mr. Potato Head" in the "Toy Story" films.
In February Rickles told Closer Weekly
he had no plans to retire despite his advanced age.
He said he was still operating with the same spontaneous humor he always had.
"I don't practice or write stuff down -- everything I do onstage was just made up before I went on," he said. "You can't please everyone, but I've been fortunate in that my fans are in my corner."
Rickles added that he was grateful for his continued audience after so many years in the business.
"Whether it's 10 people or 300 people, an audience is still an audience," he said. "If people keep showing up to see you, then it's still a high."