Founded in 1820 by Elisha Milton Cain, who had moved from Orange County, South Carolina to the Pine Flat area in 1817 and then to this area in 1820, Cain's Chapel became one of the oldest continuous church congregations in the River Region. Cain constructed a wood-frame building with sliding wooden windows and gave it the chapel's name. The cemetery, established in 1843, likely contains as its earliest burial a baby girl who died suddenly while her family was staying overnight with the Cains as they passed through town. In 1848, Dr. John M. Shelton donated additional land behind the church to enlarge the cemetery as part of a dowry for Mary A. Northrup, granddaughter of Elisha and Margaret Lewis Cain. The oldest graves mark infant Whittemore in 1848 and Mrs. Levina Benson in 1849. More than 783 graves are here, including veterans from the Civil War through the Vietnam War, among them privates, commanders, and a Bronze Star recipient. By 1885, Cain's Chapel belonged to the Deatsville Circuit of Methodist church riders. By 1890, members had built a white-frame church with glass windows using lumber donated by Dr. John M. and Mary Amanda Shelton. In 1950 and 1951, the congregation held services in the wood-frame parsonage, used from 1947 to 1962, while the white-frame church was dismantled. Its boards and beams were reused to build a new red brick chapel, completed in 1953 through the congregation's pay-as-you-go efforts. A second parsonage of matching red brick was completed in 1963 and later served as a daycare and then an office annex with a prayer garden. In 1975, the church added a vestibule, a fellowship hall, and a steeple atop the chapel. A 1988 renovation added memorial stained-glass windows to the chapel and vestibule. By 1993, a Family Life Center had been built with church offices, classrooms, an auditorium, and a kitchen. In 2005, the church added the James Moore Memorial Playground. In 2006, it demolished the fellowship hall for a new Worship Center completed in September 2007. The church uses both the Chapel and Worship Center for services, and church bells sound above the chapel and cemetery from the electronic Millennium Gold Carillon System dedicated on Easter Sunday, April 20, 2014. The site was listed in the Alabama Register of Landmarks and Heritage on October 25, 2018.