Clarence Henry was born in New Orleans, Louisiana, United States, in 1937, moving to the Algiers neighborhood in 1948. He started learning piano as a child, with Fats Domino and Professor Longhair being his main influences. When Henry played in talent shows, he dressed like Longhair and wore a wig with braids on both sides. He joined Bobby Mitchell & the Toppers in 1952, playing piano and trombone, before leaving when he graduated in 1955 to join saxophonist Eddie Smith's band.
He used his trademark croak to improvise the song "Ain't Got No Home" one night in 1955. Chess Records' A&R man Paul Gayten heard the song, and had Henry record it in Cosimo Matassa's studio in September 1956. Initially promoted by local DJ Poppa Stoppa, the song eventually rose to number 3 on the national R&B chart and number 20 on the US pop chart. The gimmick earned Henry his nickname of 'Frogman' and jump-started a career that endures to this day.
He toured nationally with a six-piece band until 1958, and continued to record. A cover of Bobby Charles' hit "(I Don't Know Why) But I Do", and "You Always Hurt the One You Love", both from 1961, were his other big hits.

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