Cooke was born Samuel Cook in Clarksdale, Mississippi, in 1931. In 1957 he added an "e" at the end of his name to signify a new start to his life. He was the fifth of eight children of the Rev. Charles Cook, a minister in the Church of Christ (Holiness), and his wife, Annie Mae. One of his younger brothers, L.C. (1932-2017), later became a member of the doo-wop band Johnny Keyes and the Magnificents.  The family moved to Chicago in 1933. Cooke attended Doolittle Elementary and Wendell Phillips Academy High School in Chicago, the same school that Nat "King" Cole had attended a few years earlier. Sam Cooke began his career with his siblings in a group called the Singing Children when he was six years old. He first became known as lead singer with the Highway QC's when he was a teenager, having joined the group at the age of 14. During this time, Cooke befriended fellow gospel singer and neighbor Lou Rawls, who sang in a rival gospel group.  In 1950, Cooke replaced gospel tenor R. H. Harris as lead singer of the gospel group the Soul Stirrers, founded by Harris, who had signed with Specialty Records on behalf of the group. Their first recording under Cooke's leadership was the song "Jesus Gave Me Water" in 1951. They also recorded the gospel songs "Peace in the Valley", "How Far Am I from Canaan?", "Jesus Paid the Debt" and "One More River", among many others, some of which he wrote. Cooke was often credited for bringing gospel music to the attention of a younger crowd of listeners, mainly girls who would rush to the stage when the Soul Stirrers hit the stage just to get a glimpse of Cooke.

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In 1957 he added an "e" at the end of his name to signify a new start to his life.