Chayefsky was born in The Bronx, New York City to Russian Jewish immigrants Harry and Gussie Stuchevsky Chayefsky who came from Moscow to New York in 1907. He had two older brothers, William and Isidor. He spent part of his youth in Mount Vernon, New York.

Returning to the United States, Chayefsky worked in his uncle's print shop, Regal Press, an experience which provided a background for his later teleplay, Printer's Measure (1953), as well as his story for the movie As Young as You Feel (1951). Kanin enabled Chayefsky to spend time working on his second play, Put Them All Together (later known as M is for Mother), but it was never produced. Producers Mike Gordon and Jerry Bressler gave him a junior writer's contract. He wrote a story, The Great American Hoax, which sold to Good Housekeeping but was never published.  He relocated to Hollywood, where he met his future wife Susan Sackler, and the couple married in February 1949. Failing to find work on the West Coast, Chayefsky returned to New York.  During the late 1940s, he began working full-time on short stories and radio scripts, and during that period, he was a gagwriter for radio host Robert Q. Lewis. Chayefsky later recalled, "I sold some plays to men who had an uncanny ability not to raise money." During 1951-52, Chayefsky wrote adaptations for radio's Theater Guild on the Air: The Meanest Man in the World (with James Stewart), Cavalcade of America, Tommy (with Van Heflin and Ruth Gordon) and Over 21 (with Wally Cox).  His play The Man Who Made the Mountain Shake was noticed by Elia Kazan, and his wife, Molly Kazan, helped Chayefsky with revisions. It was retitled Fifth From Garibaldi but was never produced. In 1951, the movie As Young as You Feel was adapted from a Chayefsky story.

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During the late 1940s, he began working full-time on short stories and radio scripts,