The Church of the United Brethren in Christ originated in the late 1700s among German immigrants in Pennsylvania, Maryland, and Virginia, including members of the Reformed Church and former Mennonites. The official founding of the church came in 1800, and the first general conference of clergy was held in 1815. Like the Methodists, the United Brethren emphasized the doctrine of justification by faith alone, but combined this with a strong emphasis on holy living. The major goal of the early pastors was saving souls. There was little emphasis on social gospel.

German-American settlers moving into Western Virginia from Maryland and the Shenandoah Valley either brought their United Brethren beliefs with them or were converted by traveling ministers. Church founder Philip William Otterbein made several trips into the mountains, but Christian Newcomer (1749-1830) founded and nurtured many of the churches in northern West Virginia.

D. C. Topping came from Ohio and established the church's Virginia Mission in Cabell County in 1835. Two years later it was renamed the Guyandotte Circuit. In 1836, the Virginia Conference sent Michael Moses to the vicinity of New Haven in Mason County. Moses established the Jackson Mission in Mason and Jackson counties. The first permanent UB church was built in 1847 at Sand Hill near Point Pleasant, described as a "good-sized frame church" with a side door that led to a "separate apartment for slaves."

An important early UB evangelist was Benjamin Stickley. He was converted by the preaching of Michael Moses and licensed in 1840. For years he traveled throughout present northern West Virginia establishing churches. Also in 1840, German members of Otterbein's church in Baltimore migrated to Braxton County and formed UB churches with John Engle as the pastor. In 1846, the churches in Lewis, Upshur, Barbour, and Gilmer counties were merged with those in Braxton County to form the Lewis or Buckhannon Circuit with Stickley as pastor.

In 1857, the Virginia Conference approved the creation of the Parkersburg Conference for the area now known as West Virginia. The conference initially included 11 preachers, 10 charges or circuits, and 1,327 members. In 1897, the name was changed to the West Virginia Conference.

The United Brethren were a pioneering denomination in allowing women to preach. As early as the 1850s, a few women were preaching, and at the 1889 General Conference a formal statement allowing women's ordination was made.

That year, however, also saw a division within the denomination. Conflicts split the church into two blocs, the smaller of which was led by Bishop Milton Wright, the father of Orville and Wilbur Wright. Both groups continued to use the name "Church of the United Brethren in Christ" until 1946. In 1946, the larger bloc merged with the Evangelical Association, forming the Evangelical United Brethren Church. At the time of the merger United Brethren churches existed primarily in two areas of West Virginia: the Ohio River counties of Cabell, Mason, Jackson, Wood, Pleasants, and Tyler, and the interior counties of Gilmer, Lewis, Upshur, Barbour, and Braxton. There were few, if any, south of a line from Huntington to Charleston and few in the eastern part of the state. At the time of the 1946 merger there were 261 United Brethren churches in West Virginia and only four congregations of the Evangelical Association.

In 1968 the Evangelical United Brethren Church merged with the Methodists to create the United Methodists, the largest Protestant denomination in West Virginia. At the time of the 1968 merger there were 240 EUB churches in West Virginia with a total membership of 23,911.

The faction of the church that was once led by Bishop Wright continues today as the Church of the United Brethren, headquartered in Huntington, Indiana. The denomination has about 200 congregations in the United States, including five in West Virginia.