While certain religions predominate, West Virginia has a diversity of religious beliefs, practices, and expressions. In 2000, there were 4,139 churches, synagogues, mosques, and temples in the state. The number of adherents of all religious faiths was 650,016, which was 35.9 percent of the state's total population. This is a considerably lower rate of religious affiliation than for the nation as a whole, which had 50.2 percent religious adherence in 2000.

West Virginians professing a religion were overwhelmingly Christian and very largely Protestant. The largest denomination was United Methodist, which accounted for 8.3 percent of the total state population and 23.2 percent of religious adherents. There were 1,341 Methodist churches, with 150,985 adherents. American Baptist USA had 463 churches with 108,087 adherents, accounting for 6.0 percent of the population and 16.6 percent of all adherents. Roman Catholics accounted for 5.8 percent of the population and 16.2 percent of all adherents, with 149 churches and 105,363 adherents. There were 11 other Christian denominations counting 10,000 or more adherents each, including numerous holiness, pentecostal, and evangelical believers. There were also small Jewish and Muslim populations, and others adhering to non-Western religions.

West Virginia's religious makeup is a product of the state's history. As early settlers ventured into the western wilderness, religious beliefs and practices journeyed with them. These settlers included many Scotch-Irish, which suggests that Presbyterianism was the dominant form of Christianity in the early years. During the Second Great Awakening (1790—1830), however, the Baptists and Methodists gained thousands of converts, and have been the largest Christian denominations in West Virginia ever since.

Energetic Methodist missionary Francis Asbury had already begun his travels throughout the region in the late 18th century. Methodist circuit riding, in which itinerant preachers traveled by horseback from congregation to congregation, spread the message and helped Methodism to flourish. Baptist, Presbyterian, and Episcopal churches developed slowly in the late 18th century and expanded their mission in the 19th century. Unique to the Northern Panhandle was the development of a new denomination, the Disciples of Christ, and Roman Catholicism first flourished there, as well.

During and before the Civil War, several denominations split due to various positions on slavery and states' rights. Although West Virginia's statehood came about for mostly secular reasons, clergy and lay leaders were frequently present at statehood conventions. Particularly influential were members of the Methodist Episcopal Church, the "Northern" Methodists. They held considerable political power in the early years of the state, their numbers including Governor Boreman and early U.S. senators and congressmen.

Methodists were also prominent in the establishment of the education system, including the public schools. When West Virginia University's first president, Alexander Martin, a Methodist minister, was fired during a political purge, the Methodists boycotted the school for a time. West Virginia's Methodist Conference later founded its own educational institution, West Virginia Wesleyan College, in Buckhannon.

Other denominations have historical ties to institutions of higher education throughout the state, although the relationships have in some cases lapsed. These institutions include Bethany College (Disciples of Christ), Salem College, now Salem International University (Seventh-Day Baptist), Morris Harvey College, now University of Charleston (Methodist), Alderson-Broaddus College (American Baptist), Ohio Valley College (Church of Christ), Wheeling Jesuit University (Roman Catholic), and Davis & Elkins College (Presbyterian).

After the Civil War, West Virginia's previously agrarian economy became increasingly industrial. Wheeling, the Northern Panhandle, and the Monongahela Valley developed strong manufacturing bases, and extractive industry claimed much of the rest of the state. Both manufacturing and extractive industries needed more workers than were present in the native population, and growing numbers of newcomers were attracted to the state.

Many immigrants from southern and eastern Europe, often Catholics, settled in the mining and manufacturing regions. Bishop Patrick J. Donahue (1894—1922) oversaw the development of numerous churches and missions, as well as schools, hospitals and orphanages to serve a growing Catholic population. Catholic parishes flourished in the southern coalfields as well as the industrial north, and Catholic communities developed in other areas as well.

Eastern European immigrants took jobs in manufacturing and mining, some of them establishing Eastern Orthodox congregations. Today there are active Orthodox congregations in Morgantown, Wheeling, Charleston, and elsewhere. Sizable numbers of Jews immigrated to West Virginia during the same period, and synagogues were established throughout the state. Muslims came as well, initially living quietly among mostly Christian neighbors. Their numbers increased in the 20th century, and mosques were established in South Charleston and elsewhere.

According to the late West Virginia University scholar Manfred Meitzen, the religious life of the newly created state was "characterized by biblical literalism, fundamentalistic morality, revivalism, and the preeminence of Protestantism." While allowing for diversity and exceptions, these characteristics still apply to a considerable extent. Many Appalachian scholars have noted the distinctly Protestant nature of the region, marked by a strongly Puritan code of ethics.

Christian faith in West Virginia has often focused on individualistic piety rather than a well-developed social gospel. Often this became manifest through non-denominational family chapels and community churches. Even among these unaffiliated congregations a strong Baptist polity often prevails, emphasizing localized control, unsupervised clergy, biblical literalism, and the power of the Holy Spirit. Fervent preaching focuses on otherworldly salvation and charismatic gifts. Salvation through Jesus Christ is rarely connected to social action. Bedrock fundamentalism takes exotic expression in some cases, including serpent handling and speaking in unknown tongues, while others profess very old beliefs such as predestinarianism.

While its overall contours remain Christian and Protestant, West Virginia's religious landscape continues to change. Groups once uncommon in the state made inroads in the 20th century, including Jehovah's Witnesses and, more recently, the Mormons. Once-dominant mainstream churches have lost membership, as elsewhere in the country, while large and often independent evangelical "megachurches" have grown. West Virginians continue to attend church at lower rates than other Americans, but it is likely that a majority of Mountaineers, churched and unchurched, still subscribe to the fundamentalist creed that Professor Meitzen said characterized that state at its creation.