The Appalachian glass industry was a quiet giant for most of the twentieth century. Lewis County had everything the industry needed: abundant natural gas (cheap fuel for furnaces), high-quality silica sand (the raw material), railroads (for moving fragile finished product), and a skilled workforce trained across generations of factory employment. Plants like Weston Glass, Davis Lynch, Tygart Valley, and a dozen others turned out cut glass, pressed glass, stemware, novelty pieces, lampshades, and industrial product. Many of the workers belonged to the American Flint Glass Workers Union of North America, one of the older and more durable industrial unions in the country. The workforce was overwhelmingly male; the labor was hot, dangerous, and skilled; the wages were comparatively good. Through the middle decades of the century, the typical Lewis County household had at least one breadwinner in glass.

The decline came slowly and then all at once. Cheap imported glass from Eastern Europe and Asia undercut American producers through the 1970s and 1980s. Plants closed in waves; equipment was scrapped or sold off; the people who knew how to make hand-blown stemware retired without successors. By 1990 the Lewis County glass industry was nearly extinct. Dean Six, a West Virginia entrepreneur and glass researcher who had spent years documenting the state's glass production, recognized that without a deliberate effort, the entire history would disappear with the last workers. He proposed a major glass museum in the state. The idea came to the attention of Merle Moore, director of the Lewis County Chamber of Commerce, who invited Six to Weston. A 1992 study group of glass-industry veterans, civic leaders, and state officials recommended that plans be drawn up to create a museum.

The Weston Area Glass History and Study Group formed in May 1992. It was a frankly amateur coalition - retired glassworkers, collectors, history enthusiasts - and that turned out to be its strength. The group raised money, bought historical glass pieces destined for the eventual museum, and pushed hard for incorporation. The West Virginia Museum of American Glass, Ltd., received its state charter on May 7, 1993, and its federal 501(c)(3) tax exemption in 1994. A 1995 proposal to house the museum in the spectacular abandoned Weston State Hospital complex - the Trans-Allegheny Lunatic Asylum - fell through. The museum opened instead on April 25, 1998, in the former Cain's Drug Store at the corner of Main and Second Streets, with 800 square feet of display space. Within eight years the collection had outgrown that space. In September 2006 the museum bought the former JCPenney's department store at 230 Main Avenue, where it has been ever since.

The collection now spans the nineteenth century through the present. Some 20,000 pieces of American glass are on public display, with at least that many more in open storage available for research. Notable holdings include Steuben Glass from the estate of Broadway producer Martin Massman; cameo glass by the West Virginia artist Kelsey Murphy; and paperweights from the defunct Degenhart Museum of Cambridge, Ohio. The Dorothy B. Dagherty Research Library holds several thousand reference books, complete proceedings of the American Flint Glass Workers Union conventions from 1878 to 1996, and the union's monthly magazine The American Flint from 1910 to 2000 - a unique combined archive of both glass production and American industrial labor history. The museum also maintains a virtual collection of more than 34,000 glass objects online, photographed and cataloged for researchers around the country. The 2008 name change to The Museum of American Glass in West Virginia formally recognized that the institution had grown beyond its original Lewis County focus.

The museum is also an active scholarly center. The annual Glass Gathering, a two-day research conference held every other year in Weston and on alternating years at sites around the country, has been the principal meeting of American glass historians since 1992. The American Mid Century Modern Glass Symposium covers a more specific era. The Ancient and Honorable Order of Glass Flakes - an invitation-only group of internationally known glass researchers and authors - holds its meetings here as well. The museum publishes a quarterly magazine, All About Glass, and has issued more than 150 monographs on specific glass topics, plus ten longer book titles under its Glass Flakes Press imprint since 2013. For a small museum in a small town in central West Virginia, the Museum of American Glass has become the principal institutional anchor for a field of study that without it would lack a center of gravity at all.