The Southern Union Conference was organized April 9, 1901, as the first of six North American districts. Located in Nashville, Tennessee, the Union began with three conferences - Cumberland, Florida, and Tennessee River - and a mission field of six states. During its first summer, five more conferences were organized: Alabama, Carolina, Georgia, Louisiana and Mississippi.

Shortly after its formation, the Southern Union adopted the Southern Missionary Society, and the Southern Publishing Association was established, publishing the Southern Watchman (later to become These Times). In 1908 the eastern half of the union separated to form the Southeastern Union Conference, and in 1909 the Southern Missionary Society was succeeded by the Southern Union Mission, which was dedicated to fostering growth among the African-American community.

A re-formation came in 1932, when the Southern and Southeastern Unions reunited and established headquarters in Decatur, Georgia. At that time the Louisiana Conference was assigned to the Southwestern Union. This is also when the Southern Tidings debuted as the official organ of the Southern Union.

Another opportunity for growth came in 1946 when the South Central and South Atlantic Conferences were added. The final conference, Southeastern, was formed in 1981 when the South Atlantic territory was divided. Currently, eight conferences comprise the Southern Union: Carolina, Florida, Georgia-Cumberland, Gulf States, Kentucky-Tennessee, South Atlantic, South Central, and Southeastern.

The year 2001 witnessed the 100th anniversary of the Union, a century of both progress and growth. A 100th anniversary celebration drew crowds of approximately 5,000 to Atlanta in September, despite happening on the heels of the 9-11 tragedy.

Currently the second largest union, the Southern Union continues to experience rapid growth in membership and tithe, as it serves its constituent conferences and Church members.