Cohan was born in 1878 in Providence, Rhode Island, to Irish Catholic parents. A baptismal certificate (which gave the wrong first name for his mother) indicated that he was born on July 3, but Cohan and his family always insisted that George had been "born on the Fourth of July!" George's parents were traveling vaudeville performers, and he joined them on stage while still an infant, first as a prop, learning to dance and sing soon after he could walk and talk.

Cohan began his career as a child, performing with his parents and sister in a vaudeville act known as "The Four Cohans." Beginning with Little Johnny Jones in 1904, he wrote, composed, produced, and appeared in more than three dozen Broadway musicals. Cohan published more than 300 songs during his lifetime, including the standards "Over There," "Give My Regards to Broadway," "The Yankee Doodle Boy" and "You're a Grand Old Flag." As a composer, he was one of the early members of the American Society of Composers, Authors, and Publishers (ASCAP). He displayed remarkable theatrical longevity, appearing in films until the 1930s, and continuing to perform as a headline artist until 1940.