Pope Pius IX on July 19, 1850, erected the Diocese of Wheeling, containing the area of Virginia south of the Pennsylvania state border and west of the Allegheny Mountains.

After 18 years, Leo XIII named Kain as coadjutor archbishop of the Archdiocese of St. Louis in 1893 and appointed Reverend Patrick Donahue of Baltimore as the new bishop of Wheeling in 1894.

"[7] In 1922, Pope Pius XI appointed Reverend John Swint as an auxiliary bishop of Wheeling.

While the diocese had long served the Italian, Irish, and Polish immigrant groups, the major population growth came during Swint's tenure.

He oversaw the building of a new cathedral, 100 churches, Wheeling Jesuit College, 52 elementary and high schools, and five hospitals.

He said it was part of a national plan by doctors to break the Catholic Church's ban on artificial birth control.

He mandated parish councils in 1968, introduced extraordinary ministers to the diocese in 1970 and permanent deacons in 1975, and renovated the exterior and interior of St. Joseph's Cathedral in Wheeling in 1973.

A year later, John Paul II appointed Schulte as archbishop of the Archdiocese of New Orleans and replaced him in West Virginia with Schmitt.

Schmitt resigned in 2004 and John Paul II replaced him with Monsignor Michael J. Bransfield from the Archdiocese of Philadelphia.

On September 13, 2018, Pope Francis accepted the resignation of Bransfield and appointed Archbishop William E. Lori as apostolic administrator.

The diocese responded in September 2020 that it had reviewed Golebiewski's allegations, determining that they were not credible; it gave no reasons for his dismissal.

The Diocese of Wheeling-Charleston owns a multi-million dollar investment portfolio that it received as a donation by Sara Tracy in the early 20th century.

[18] Reverend Felix Owino, a professor at Wheeling Jesuit University, pleaded guilty in September 2010 to inappropriately touching an 11-year-old girl.

[24] Morrisey said that the diocese advertised itself as a safe place for children while "knowingly employed pedophiles and failed to conduct adequate background checks" on workers in Catholic schools and camps.

[24] The lawsuit was groundbreaking because it named a diocese as a defendant, rather than individual priests, and because it sought to make use of consumer-protection law to obtain legal discovery of church records.

[25] In November 2020, the West Virginia Supreme Court ruled that the consumer protection law did not apply to the diocese.

[26] Four lawsuits were filed against the diocese in 2020 regarding Reverend Victor Frobas, a teacher at St. Paul's Catholic School in Weirton in the early 1980s.

The lawsuit noted that the diocese was aware of sexual abuse allegations against Frobas from when he previously served in the Archdiocese of Philadelphia as well as in Weirton.

In 1988, Frobas pleaded guilty to sexually molesting boys in Kirkwood, Missouri and was sentenced to four years in prison there.

Also in November 2019, Brennan revoked some of Bransfield's retirement benefits and barred him from being buried in the diocesan cemetery.