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The first branch of Christianity to gain a foothold in Indiana was Roman Catholicism, introduced by the French settlers in the early 18th century. The first Protestant church was founded near Charlestown by Baptists from Kentucky in 1798. Three years later, a Methodist church was organized at Springville; in 1806, Presbyterians established a church near Vincennes; and the following year, Quakers built their first meetinghouse at Richmond. The Disciples of Christ, Lutherans, the United Brethren, Mennonites, and Jews were among the later 19th-century arrivals.

A dissident religious sect, the Shakers, established a short-lived community in Sullivan County in 1808. In 1815, some German separatists, led by George Rapp, founded a community called the Harmonie Society, which flourished briefly. Rapp moved his followers to Pennsylvania and sold the town to a Scottish social reformer, Robert Owen, in 1825. Owen renamed the town New Harmony and tried to establish a nonreligious utopia there, but the experiment failed after three years. A group of religious dissidents founded the Pentecostal Church of God at Beaver Dam in 1881; the world headquarters of the church, which had 101,921 adherents nationwide in 2000, is now at Anderson. The Youth for Christ movement started in Indianapolis in 1943.

In 2000, the Roman Catholic Church was the largest single denomination with about 836,009 adherents in 462 congregations. The largest Protestant denominations were the United Methodist Church (with 288,308 adherents in 1,286 congregations), the Church of Christ (205,408 adherents), the Southern Baptist Convention (124,452), the American Baptist Church (115,101), and the Lutheran Church—Missouri Synod (111,522). The estimated Jewish population of the state in 2000 was 18,000, down from 20,314 members in 1990. The Muslim community had about 11,000 members in 2000. There were also over 17,000 Mennonites and over 19,000 members of Amish communities statewide. About 57% of the population (over 3.4 million people) were not counted as members of any religious organization.