The Methodist Episcopal Church, South (MEC, S; also Methodist Episcopal Church South) was the American Methodist denomination resulting from the 19th-century split over the issue of slavery in the Methodist Episcopal Church (MEC). Disagreement on this issue had been increasing in strength for decades between churches of the Northern and Southern United States; in 1845 it resulted in a schism at the General Conference of the MEC held in Louisville, Kentucky.

This body maintained its own polity for nearly 100 years until the formation in 1939 of the Methodist Church, uniting the Methodist Episcopal Church, South, with the older Methodist Episcopal Church and much of the Methodist Protestant Church, which had separated from Methodist Episcopal Church in 1828. The Methodist Church in turn merged in 1968 with the Evangelical United Brethren Church to form the United Methodist Church, one of the largest and most widely spread Christian denominations in America.

In 1940, some more theologically conservative MEC,S congregations, which dissented from the 1939 merger, formed the Southern Methodist Church, which still exists as a small, conservative denomination headquartered in South Carolina. Some dissenting congregations from the Methodist Protestant Church also objected to the 1940 merger and continue as a separate denomination, headquartered in Mississippi.

John Wesley, the founder of Methodism, was appalled by slavery in the British colonies. When the Methodist Episcopal Church (MEC) was founded in the United States at the "Christmas Conference" synod meeting of ministers at the Lovely Lane Chapel in Baltimore in December 1784, the denomination officially opposed slavery very early. Numerous Methodist missionaries toured the South in the "Great Awakening" and tried to convince slaveholders to manumit the people whom they enslaved. In the first two decades after the American Revolutionary War, a number did free people from slavery. The number of free blacks increased markedly at this time, especially in the Upper South.

During the early nineteenth century, Methodists and Baptists in the South began to modify their approach in order to gain support from common planters, and yeomen. They began to argue for better treatment of slaves, saying that the Bible acknowledged slavery but that Christianity had a paternalistic role to improve conditions.

The invention of the cotton gin had enabled profitable cultivation of cotton in new areas of the South, increasing the demand for slaves. Manumissions nearly ceased and, after slave rebellions, the states made them extremely difficult to accomplish. Northern Methodist congregations increasingly opposed slavery, and some members began to be active in the abolitionist movement. The southern church accommodated it as part of a legal system.

But, even in the South, Methodist clergy were not supposed to own slaves. In 1840, the Rev. James Osgood Andrew, a bishop living in Oxford, Georgia, bought a woman. Fearing that she would end up with an inhumane owner if sold, Andrew kept her but let her work independently.^{[citation needed]} The 1840 MEC General Conference considered the matter, but did not expel Andrew. Four years later, Andrew married a woman who owned a slave inherited from her mother, making the bishop the owner of two people. As bishop, he was considered to have obligations both in the North and South and was criticized for owning slaves.

The 1844 General Conference voted to suspend Bishop Andrew from exercising his episcopal office until he was no longer a slave owner. Southern delegates to the conference disputed the authority of a General Conference to discipline bishops. The cultural differences that had divided the nation during the mid-19th century were also dividing the Methodist Episcopal Church. The 1844 dispute led Methodists in the South to break off and form a separate denomination, the Methodist Episcopal Church, South (MEC,S). Delegates from the southern conferences met at a Convention at the Fourth Street Church in Louisville, Kentucky, May 1–19, 1845, and organized the Methodist Episcopal Church, South.