The first religious settlement in Ohio territory was founded among Huron Indians in 1751 by a Roman Catholic priest near what is now Sandusky. Shortly afterward, Moravian missionaries converted some Delaware Indians to Christianity; the first Protestant church was founded by Congregationalist ministers at Marietta in 1788. Dissident religious sects such as the Shakers, Amish, and Quakers moved into Ohio from the early 18th century onward, but the majority of settlers in the early 19th century were Presbyterians, Methodists, Baptists, Disciples of Christ, and Episcopalians.

The first Roman Catholic priest to be stationed permanently in Ohio was Father Edward Fenwick, who settled in Cincinnati in 1817. When the Protestant settlers there did not allow him to build a Catholic church in the town, he founded Christ Church (now St. Francis Church) just outside Cincinnati. In 1821, Father Fenwick became the first Catholic bishop in Ohio. The large influx of Irish and German immigrants after 1830 greatly increased the Catholic constituency in Cleveland, Cincinnati, Columbus, and Toledo. Among the German immigrants were many Lutherans and large number of Jews, who made Cincinnati a center of Reform Judaism. In the mid-19th century, Cincinnati had the nation's 3rd-largest Jewish community; the Union of American Hebrew Congregations, the most important Reform body, was founded there in 1873, and Hebrew Union College, a rabbinical training school and center of Jewish learning, was founded two years later. The Church of Jesus Christ of Latter-Day Saints (Mormons), founded in 1930 by Joseph Smith, Jr. of New York, built its first permanent place of worship in Kirtland, Ohio, in 1933. The Kirtland Temple, as it has been called, is still open today.

In 2000, Ohio had a Roman Catholic population of about 2,231,832. During the same year, the state's Jewish population was estimated at 142,255. Leading Jewish communities were in Cleveland, Cincinnati, and Columbus. The Muslim population was at about 41,281 people. Ohio communities of Amish and Mennonites are among the largest in the nation with over 24,000 Amish and over 20,000 Mennonites in the state (primarily central Ohio).

The largest Protestant denominations and their adherents in 2000 were the United Methodist Church, 566,084; the Evangelical Lutheran Church in America, 301,749; the Southern Baptist Convention, 187,227; the Presbyterian Church USA, 160,800; the United Church of Christ, 157,180; Christian Churches and Churches of Christ, 142,571; and the American Baptist Churches USA, 117,757. About 6.2 million people (55.1% of the population) were not counted as members of any religious organization.