Tributes poured in online, including from actor Josh Gadd, who called Reiner "one of the greatest comedic minds of all time", and writer Bill Kristol, who said: "What a life!"
Reiner also created and starred in the Dick Van Dyke Show.
Reiner's assistant Judy Nagy said he died of natural causes Monday night at his home in Beverly Hills, Calif. Reiner also scored a major TV hit by creating and co-writing The Dick Van Dyke Show, starring the popular entertainer, before going on to achieve renown as the director of Steve Martin's best known films.
In 2018, at age 96, Reiner became the oldest Emmy nominee in history for his narration of the HBO documentary "If You're Not in the Obit, Eat Breakfast".
Carl is survived by his children Rob, Lucas and Annie, according to Variety.
Reiner expressed his approach to his work in his book My Anecdotal Life, when he said, "Inviting people to laugh at you while you are laughing at yourself is a good thing to do. You may be the fool but you are the fool in charge". Taking an interest in acting as a teenager, Reiner was later performing on stage for troops during his stint with the Army Air Forces in the 1940's.
Carl Reiner was born on March 20, 1922 and grew up in The Bronx, New York.
In his 90s, virtually every day in Beverly Hills, Reiner met with Brooks, after they both lost their wives, and they would sit on Reiner's sofa watching movies, telling jokes and recalling a lifetime of comedy.
Asked why the cross became a symbol for Christianity, for example, Brooks replied: "It was easier to put together than the Star of David".
"Getting to work with Carl Reiner on Two and a Half Men was one of the most rewarding and joyful experiences of my career", Lorre told Deadline. He would go on to appear in shows titled Inside U.S.A. and Alive and Kicking on Broadway.
Other Hollywood celebrities also reacted to the news of Reiner's passing via social media including Jason Alexander and Alan Alda. In the 1990s, he reprised the Alan Brady character for an episode of Mad About You.
Dick Van Dyke, star of Reiner's classic sitcom "The Dick Van Dyke Show", offered his condolences.
Though Reiner made some notable on-screen appearances, his career was largely based behind the camera as a writer, director and producer.
His film credits included directing George Burns in 1977's Oh, God! and Steve Martin in The Jerk, Dead Men Don't Wear Plaid and The Man with Two Brains.