Betty Comden was born Basya Cohen in Brooklyn, New York in 1917, the younger child of Leo Cohen (originally Astershinsky), a lawyer, and Rebecca (née Sadvoransky) Cohen, an English teacher. Both were Russian immigrants and observant Jews. She had an older brother, Nathaniel ("Nat"), born c. 1915. Basya "attended Erasmus Hall High School and studied drama at New York University, graduating in 1938," according to The New York Times.
In 1938, mutual friends introduced her to Adolph Green, an aspiring actor. Along with the young Judy Holliday and Leonard Bernstein, Comden and Green formed a troupe called the Revuers, which performed at the Village Vanguard, a club in Greenwich Village. Due to the act's success, the Revuers appeared in the 1944 film Greenwich Village, but their roles were so small they were barely noticed, and they returned to New York.
Comden and Green's first Broadway show was in 1944, with On the Town, a musical about three sailors on leave in New York City that was an expansion of a ballet entitled Fancy Free on which Bernstein had been working with choreographer Jerome Robbins. Comden and Green wrote the book and lyrics, which included sizable parts for themselves (as "Claire" and "Ozzie"). Their next musical, Billion Dollar Baby in 1945, with music by Morton Gould was not a success, and their 1947 show Bonanza Bound closed out-of-town and never reached Broadway.

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