Baptist and Presbyterian churches were organized on the frontier soon after permanent settlements were made. Many divisions have occurred in both groups. The Cumberland Presbyterian Church, which spread into other states, was organized near Nashville in 1810 because of differences within the parent church. Both the Baptists and the Presbyterians divided over slavery. Methodist circuit riders arrived with the early settlers, and they quickly succeeded in attracting many followers. Controversies over slavery and other sectional issues also developed within the Methodist Church and, as with the Baptists and Presbyterians, divisions emerged during the 1840s. The Methodists, however, were able to resolve their differences and regroup. The United Presbyterian Church and the Presbyterian Church in the US finally ended their 122-year separation in 1983, reuniting to form the Presbyterian Church (USA).

Two other Protestant groups with large followings in the state had their origin on the Tennessee frontier in the first half of the 19th century: the Disciples of Christ and the Church of Christ. Both groups began with the followers of Thomas and Alexander Campbell and Barton W. Stone, among others, who deplored formal creeds and denominations and sought to return to the purity of early Christianity. As their numbers grew, these followers divided into Progressives, who supported missionary societies and instrumental music in church, and Conservatives, who did not. In 1906, a federal census of religions listed the Conservatives for the first time as the Church of Christ and the Progressives as the Disciples of Christ. The latter, now the Christian Church (Disciples of Christ) had 28,108 known adherents in 2000. The Church of God (Cleveland, Tennessee) was established in the state in 1886 as a result of the greater Pentecostal movement.

Tennessee has long been considered part of the Bible Belt because of the influence of fundamentalist Protestant groups that believe in the literal accuracy of the Bible. Evangelical Protestants still account for a majority of the religiously active population. In 2000, the largest single religious group in the state was the Southern Baptist Convention with 1,414,199 adherents. Other Evangelical groups were the Churches of Christ, 216,648; the Church of God (Cleveland, Tennessee), 66,136; Independent, Non-Charismatic Churches, 50,003; and Assemblies of God, 40,430. The major Mainline Protestant denominations were the United Methodist Church, 393,994; the Presbyterian Church USA, 67,800; and the Episcopal Church, 35,037. There were 183,161 Roman Catholics, 18,464 Muslims, and an estimated 18,250 Jews in the state. About 2.7 million people (48,9% of the population) were not counted as members of any religious organization.