Lutheranism traces directly from the Reformation work of Martin Luther and its doctrinal statements, the Augsburg Confession (1530) and the Book of Concord. Having spread across northern Europe, Lutheranism came to America in waves of immigration over two centuries. This resulted in a sometimes confusing multiplicity of church synods, as early immigrants changed and acculturated while newer ones held to the familiar traditions from their home countries.

Lutherans entered Western Virginia in the 1730s, as Pennsylvania Germans migrated down the Shenandoah Valley. Mecklenburg (now Shepherdstown) was chartered in 1762, and German craftsmen populated the town's German Street. St. Peter's Lutheran Church was established in 1765, and others followed. When the Roush family moved west to present Mason County and called the Reverend Paul Henkel, a prominent early mission developer, to visit in 1806, Lutheranism reached the Ohio River. By 1809, the Lutheran churches of Virginia, under the parent Ministerium of Pennsylvania, numbered 48. Twelve of them were within the present territory of West Virginia, from Martinsburg to Lewisburg, plus Mason County in the west.

A second cluster of "mountaintop" churches developed along northern transportation routes. St. Paul's in Aurora, Preston County (1787), and St. John's in Red House, in neighboring Garrett County, Maryland (1790), began a community of congregations serving mountain farming communities. The National Road and then the Baltimore & Ohio Railroad spread congregations to locations such as Wheeling, Grafton, Elkins, and Davis. By the end of the 19th century, industrial Wheeling held the largest concentration of Lutherans in West Virginia. Lutherans from Ohio spread up the Kanawha River, bringing the first congregation, St. Paul's, to Charleston in 1892.

Often isolated and individualistic, West Virginia Lutherans nevertheless developed a distinctive family feeling of mutual support. As controversies over doctrinal statements and the use of English subsided in the 20th century, national mergers have brought most Lutherans together. Most West Virginia Lutheran congregations are affiliated with the Evangelical Lutheran Church in America, with a few other congregations belonging to the Missouri Synod. Significant 20th century leaders of the church in West Virginia include Dr. Donald D. Anderson, Dr. W. P. Cline, Dr. W. Roy Hashinger, Dr. Beryl B. Maurer and the Reverend George C. Weirick. By 2002, the West Virginia-Western Maryland Synod of the Evangelical Lutheran Church in America claimed 15,488 baptized members in 62 congregations.