Clarence Williams was born in Plaquemine, Louisiana. He ran away from home at age 12 to join Billy Kersand's Traveling Minstrel Show, then moved to New Orleans. At first Williams worked shining shoes and doing odd jobs, but soon became known as a singer and master of ceremonies. By the early 1910s he was a well regarded local entertainer also playing piano, and was composing new tunes by 1913. Williams was a good business man and worked arranging and managing entertainment at the local African-American vaudeville theater as well as various saloons and dance halls around Rampart Street, and clubs and houses in Storyville.

Williams started a music publishing business with violinist/bandleader Armand J. Piron 1915. He toured briefly with W.C. Handy, set up a publishing office in Chicago, then settled in New York in the early 1920s. In 1921 he married blues singer and stage actress Eva Taylor with whom he would frequently perform. He supervised African-American recordings for New York offices of Okeh phonograph company in the 1920s; he was responsible for recruiting many of the artists who performed on that label. He also led bands frequently for Columbia and occasionally other record labels. He also produced and participated in early recordings by Louis Armstrong, Sidney Bechet, Bessie Smith and many others.

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