Catholics first came to Western Virginia after the American Revolution when anti-Catholic laws were ended. Small Catholic communities started in places like Wheeling and in the Eastern Panhandle.

A big change happened in the 1840s with the arrival of the Baltimore & Ohio Railroad, which brought many Irish Catholic workers to the area. As the number of Catholics grew, the Catholic Church created a new diocese (church district) for the area. In 1850, Pope Pius IX established the Diocese of Wheeling, with Bishop Richard Whelan in charge.

At first, the diocese's borders didn’t match the state lines. It wasn’t until 1974 that the Church adjusted the diocese’s borders to match. The name became the Diocese of Wheeling-Charleston.

As West Virginia industrialized in the late 1800s, more immigrants—Irish, German, and later people from Eastern and Southern Europe—came to work and brought their Catholic faith with them. Bishop Donahue (1894–1922) helped grow the Church by adding churches, schools, hospitals, and orphanages.

Later bishops continued this work. Bishop Swint (1922–1962) focused on building schools, hospitals, and churches. Bishop Hodges (1962–1985) helped bring in modern Church reforms from the Second Vatican Council. In recent years, the Church has faced serious problems. In 2019, Bishop Bransfield was investigated for misconduct, and new leadership was brought in.

The number of Catholics in West Virginia peaked in the 1960s at around 110,000 but dropped to under 67,000 by 2022.