The West Virginia Chamber of Commerce was established during the Great Depression. Phil Conley, editor of The West Virginia Review, is credited with organizing the state chamber. At his urging, in May 1935 a group of business leaders met at The Greenbrier in White Sulphur Springs. Additional meetings followed, culminating in the adoption of a constitution and bylaws in Parkersburg in January 1936. Richard Harte of Parkersburg was elected the first president of the state Chamber of Commerce.

The first Chamber of Commerce in America was the Chamber of Commerce of the State of New York, which traces its origins to 1768, in the colonial period. The U.S. Chamber of Commerce was founded in 1912. The national membership now includes about three million companies, nearly 3,000 state and local chapters, about 83 associations, and roughly 90 American Chambers of Commerce abroad.

Prior to the formation of the West Virginia Chamber of Commerce, various cities had their own chambers of commerce, including Huntington, whose chamber was established in 1895; Charleston, whose chamber was established in 1899; and Wheeling, whose chamber was established in 1918. Among the early objectives of the state chamber were to lobby the state legislature and Congress on matters of interest to West Virginia business; to seek favorable changes in taxation; to provide a bulletin to inform members of activity in Charleston; and to advertise the state.

The Chamber's goals are similar today. The West Virginia Chamber of Commerce has more than 50 local chambers of commerce in its membership.