The Methodist Episcopal Church, South was the so-called "Southern Methodist Church" resulting from the split in the Methodist Episcopal Church which had been brewing over several years until it came out into the open at a conference held in Louisville, Kentucky in 1845. This body maintained its own polity until it merged with the Methodist Episcopal Church and the Methodist Protestant Church to form the Methodist Church in 1939, which in turn later (1968) merged with the Evangelical United Brethren to form the United Methodist Church. Conservative Southern congregations dissenting from the merger formed the Southern Methodist Church in 1940.

During the mid-19th century (1830s-1840s), some ministers of the Methodist Episcopal Church, South began preaching sermons supporting and even encouraging slavery. The church used the stories of Ham and Cain from the Bible to enforce the message that people of color where inferior to whites. This promoted belief encouraged white males to own slaves in order to control the sinful people of color and have dominion over Africans, the "children of Ham". While this doctrine was abandonned after the American Civil War and later throughly repented of, the negative connotations associated with it led to the demand for a separate denomination for black Methodists in the South after the war, which was to become the CME Church. Some black congregations chose to remain in full fellowship with their white counterparts, however.