In the Conference Minutes of 1806 is the first listing of an appointed preacher assigned specifically to Louisville. However, Frances Asbury made several references to Louisville and Jefferson County in his Journal; the earliest date was December 8, 1801. In 1810, the Methodist, Baptists, and Presbyterians built a House of Worship, called Union Church. In 1820, the Baptists and Presbyterians left to build their facilities, and the Methodist continued in the church at Seventh and Cherry Street. This church was given to a Black congregation and moved to the country becoming Dixon's Chapel. In 1860, on land at Seventh and Peachtree Streets, a new building was erected and used until 1893 when the present building was built. Under the direction of Rev. George C. Thompson, who was also an architect, a distinctive building of Romanesque and Gothic architecture was erected. The most outstanding features are the two front windows, designed by Louis C. Tiffany. There are fifteen other Tiffany windows in the building. The pulpit area is under a Roman arch with Gothic arches on either side. Louisville was on a circuit, at the first, in the North Macon District. By 1919, it was a station church in the Dublin District.
The parsonage was started in 1961 and dedicated in 1968. In 1962, Oak Grove Methodist merged with Louisville. A Fellowship Hall was dedicated in 1984. The Annex, containing Sunday school rooms, office complex, choir room, and Library/Archives room was remodeled in 1991. In 1992, the church had active youth programs, including Junior MYF, a Handbell and Chancel Choir, UMW, and UMM groups. In 2015, the church continued to support a Thrift Store and Community Food Pantry for local mission work and a strong Youth/Children Ministry.