Reiner was born in The Bronx, New York, on March 20, 1922, to Irving and Bessie Reiner (née Mathias). He was Jewish. His father was a watchmaker from Austria, and his mother was from Romania. He had an older brother, Charles, who served in the 9th Division in World War II; his ashes are buried at Arlington National Cemetery.

When Reiner was 16, working as a machinist repairing sewing machines, Charles read about a free drama workshop sponsored by the Works Progress Administration and told him about it. Carl later credited Charles with his decision to change careers. His uncle Harry Mathias was the first entertainer in his family.
Reiner was drafted into the United States Army Air Forces on October 27, 1942, and served during World War II, eventually achieving the rank of corporal by the end of the war. He initially trained to be a radio operator. After spending three months in the hospital recovering from pneumonia, he was sent to Georgetown University for ten months of training as a French interpreter. There, he had his first experience as a director, putting on a Molière play entirely in French. After completing language training in 1944, he was sent to Hawaii to work as a teleprinter operator. The night before he was scheduled to ship out for an unknown assignment, he attended a production of Hamlet by the Special Services entertainment unit. Following an audition before actor Major Maurice Evans and Captain Allen Ludden, he was transferred to Special Services. Over the following two years, Reiner performed around the Pacific theater, entertaining troops in Hawaii, Guam, Saipan, Tinian, and Iwo Jima until he was honorably discharged in 1946.

Reiner performed in several Broadway musicals (including Inside U.S.A. and Alive and Kicking) and had the lead role in Call Me Mister. In 1950, he was cast by Max Leibman as a comic actor on Sid Caesar's Your Show of Shows, appearing on air in skits while also contributing ideas to such writers as Mel Brooks and Neil Simon. He did not receive credit for his sketch material, but won Emmy Awards in 1955 and 1956 as a supporting actor. Reiner also wrote for Caesar's Hour with Brooks, Simon, Woody Allen, Larry Gelbart, Mel Tolkin, Mike Stewart, Aaron Ruben, Sheldon Keller, and Gary Belkin. He assumed the role of head writer and semi-regular on The Dinah Shore Chevy Show during the 1959–60 television season.

In November 1958, Reiner hosted a CBS prime time game show called Keep Talking, when he succeeded original host Monty Hall. He left the show in July 1959 and was succeeded by Vincent Price.
Starting in 1960, Reiner teamed with Brooks as a comedy duo on The Steve Allen Show. Their performances on television and stage included Reiner playing the straight man in The 2000 Year Old Man. Eventually the routine expanded into a series of five comedy albums and a 1975 animated television special, with the last album in the series winning a Grammy Award for Best Spoken Word Comedy Album. The act gave Brooks "an identity as a comic performer for the first time", said Reiner. Brooks's biographer William Holtzman called their 12-minute act "an ingenious jazz improvisation..." while Gerald Nachman described Reiner's part in guiding the act:

The routine relies totally on the team's mental agility and chemistry. It's almost heresy to imagine Brooks performing it with any other straight man. Reiner was a solid straight man to Caesar, but with Brooks he is the second-banana supreme... guiding his partner's churning comic mind.

In 1958, he wrote the initial 13 episodes of a television series titled Head of the Family, based on his own personal and professional life. However, the network disliked Reiner in the lead role for unknown reasons. In 1961, the series was recast and re-titled The Dick Van Dyke Show and became a popular series, making stars of his lead actors Dick Van Dyke and Mary Tyler Moore. In addition to writing many of the episodes, Reiner occasionally appeared as show host Alan Brady. The series ran from 1961 to 1966 and thereafter entered a long run of syndication. In 1966, Reiner co-starred in The Russians Are Coming, the Russians Are Coming.

From April 5, 1964, to September 9, 1965, Reiner hosted The Celebrity Game, a CBS prime time game show that was a precursor to the long-running Hollywood Squares. His first fil…

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Reiner was the author of more than two dozen books. His first autobiographical novel Enter Laughing (1958) led to a 1995 sequel Continue Laughing. He published a memoir My Anecdotal Life: A Memoir in 2003. He also wrote a humorous series of memoirs under the titles I Remember Me (2012), I Just Remembered (2014), and What I Forgot to Remember (2015), along with books about film and art. He began to write children's books based on the stories he used to tell a certain grandson who would request, "Tell me a scary story, Grandpa, but not too scary."