The group was formed by Roy Crain, who had launched his first quartet, which sang in a jubilee style, in 1926 in Trinity, Texas. In the early 1930s, after Crain moved to Houston, he joined an existing group on the condition that it change its name to "the Soul Stirrers." Among the members of that group was R.H. Harris, who soon became its musical leader.
Harris, also from Trinity, Texas, brought several changes to the Soul Stirrers that affected gospel quartet singing generally. He used a falsetto style that may have its antecedents in African music, but which was new to the popular jubilee singing style of the time. He pioneered the "swing lead", in which two singers would share the job of leading the song, allowing virtuoso singers to increase the emotional intensity of the song as the lead passed between them. That innovation led the Soul Stirrers, while still called a quartet, to acquire five members; later groups would have as many as seven but still consider themselves "quartets", which referred more to their style than their number.
The Soul Stirrers made other important changes in those years: ad-libbing lyrics, singing in delayed time, and repeating words in the background as both a rhythmic and emotional support for the lead singers. The Soul Stirrers dropped the "flatfooted" style of jubilee quartets before them and expanded their repertoire from spirituals and traditional hymns to the newer gospel compositions. The group also loosened the rigid arrangements that jubilee quartets had favored to permit individual singers within the group more space for individual development.
In 1936 Alan Lomax recorded the Soul Stirrers for the Library of Congress's American music project. They later moved to Chicago, where they broadcast a weekly radio show. Their nationwide touring gained them an even larger audience, as they delivered the emotional fervor that popular jubilee groups, such as the Golden Gate Quartet, did not.
The Soul Stirrers signed with Specialty Records, where they recorded a number of tracks, including "By and By" and "In that Awful Hour". Harris, the most popular member of the group, soon quit, however, in order to form a new group. He was replaced by the then-unknown Sam Cooke.
One of the first singles with Cooke was "Jesus Gave Me Water", a major hit that brought the Soul Stirrers massive acclaim. Thomas L. Breuster was replaced by Bob King and, briefly, Julius Cheeks. When Cooke left in 1957 to pursue a career in pop music, the Soul Stirrers' preeminence in gospel was essentially over, though a brief period of success with Johnnie Taylor sustained the group for a time. Various line-ups continued touring and recording throughout the last half of the century to a small and devoted following. The group — and all of its members — was inducted into the Rock and Roll Hall of Fame in 1989 as one of rock's Early Influences, and into the Vocal Group Hall of Fame in 2000.