Cooke was born in Clarksdale, Mississippi. He later added an "e" onto the end of his name, though the reason for this is disputed.[8] He was one of eight children of Annie Mae and the Reverend Charles Cook, a Baptist minister. He had a brother, L.C., who some years later would become a member of the doo-wop band Johnny Keyes and the Magnificents. The family moved to Chicago in 1933. Cooke attended Wendell Phillips Academy High School in Chicago, the same school that Nat "King" Cole had attended a few years earlier.[8]
Cooke began his career singing gospel with his siblings in a group called The Singing Children when he was nine. He first became known as lead singer with the Highway QC's as a teenager joining at the age of 14. In 1950, Cooke replaced gospel tenor R.H. Harris as lead singer of the landmark gospel group The Soul Stirrers. Under Cooke's leadership, the group signed with Specialty Records and recorded the hits "Peace in the Valley", "How Far Am I From Canaan?", "Jesus Paid the Debt", and "One More River", among many other gospel songs. Cooke was often credited for bringing the attention of gospel music to 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.
In 1963, Cooke's 18 month old son, Vincent, wandered away from his mother's supervision and drowned in their front yard pool while Sam was away from the home. With their marriage already in trouble largely due to extramarital affairs by both Sam and his wife, Barbara, the distance between them deepened as Sam blamed Barbara for their son's death. Cooke retreated into a deep depression, and asked that no one wear black to the child's funeral. He found his escape in out-of-town performances, which he agreed to at every opportunity.
Cooke died at the age of thirty-three on December 11, 1964, at the Hacienda Motel at 9137 South Figueroa Street in Los Angeles, California via gunshot wound to the torso.