The modern West Virginia chemical industry began in the Kanawha Valley in the 1920s and peaked shortly after World War II. Its roots are in the salt industry of the early 1800s. In the early 1900s, chemical manufacturers were attracted to the Kanawha Valley by the presence of salt brine, coal, oil, and gas; rail and water transportation; and skilled people from the salt industry. The Belle Alkali Company started a plant near Belle in 1915 to produce chlorine, caustic, and hydrogen by electrolysis of the brine. In South Charleston, the Rollin Chemical Company built a unit to recover barium peroxide and other barium salts. E. C. Klipstein & Sons started producing sulfur dyes, tear gas, and anthraquinone in 1915. Both these companies were eventually purchased by Union Carbide.

The Warner-Klipstein Chemical Company also started up in 1915, to produce chlorine, caustic, carbon disulfide, and carbon tetrachloride. In the 1920s, it became the Westvaco Chemical Corporation, and by 1930 it was the largest chlorine producing plant in the world, using brine from 17 wells on the site. During World War II, it produced barium nitrate for incendiaries, hexachloroethane for smoke screens, and catalyst for synthetic rubber. In 1948, it became part of FMC. In 1957, FMC developed a new source of brine at Bens Run in Tyler County on the Ohio River. The highly concentrated brine was shipped by barge to South Charleston, keeping the South Charleston plant competitive until the 1990s.

Farther down the Kanawha River, in 1917, the U.S. government hired the DuPont Company to build a new nitrocellulose plant to meet the demands of World War I. The Explosives Plant "C," including the entire new town of Nitro, was built in just 11 months using a work force of up to 19,000. The plant operated for one week and then was shut down when the war ended in 1918. The property was organized as an industrial park and was sold to private companies. At least 17 different companies have located at the site over the years. The Viscose Company established a plant in 1921 to make cotton linters, a gunpowder ingredient. Viscose became American Viscose, which built a new rayon fiber unit in 1937 that became the largest staple rayon plant in the world by 1945. The plant later became Avtex Fibers, which operated until 1980. Other early companies locating in Nitro included Ohio Apex Chemical, Monsanto, Elko Chemical, the Nitro Pencil Company, the Nitro Soap Factory, and later, Fike Chemical.

In 1920, the Union Carbide Company bought a small refinery near Clendenin to experiment with promising research from the Mellon Institute in Pittsburgh. In 1925, they moved to the Rollin Chemical site in South Charleston to produce ethylene glycol antifreeze from natural gas constituents that were normally burned or discarded, creating the well-known Prestone brand. During the next 30 years, Union Carbide developed or commercialized more than 150 chemicals, including polymers such as vinyl chloride. The company also built units in Institute and created the Tech Center in South Charleston, which became its worldwide research and development center. "Carbide" as it was locally known, ushered in the age of petrochemistry at these West Virginia plants.

The 1920s also saw the startup in 1926 of the new DuPont plant at Belle, to make ammonia from coal using high-pressure synthesis. In 1927, the plant also began making synthetic wood alcohol, eventually supplying more than 40 percent of the market. The DuPont plant went on to make a number of important chemicals for the first time, including crystal urea, methyl methacrylate plastic or Lucite, nylon salt, Hypalon synthetic rubber, and Delrin acetal resin, making the site a pioneer in the new era of polymers.

World War II brought another major increase in the production of chemicals in the Kanawha Valley. In 1941, the government started a synthetic rubber program at the Institute site. The Carbide and Carbon Chemicals Corporation along with the U.S. Rubber Corporation built plants to make Buna S synthetic rubber. The first rubber was made in March 1943, at the site that later became Union Carbide's Institute plant. Nearby, the Monsanto Company was making chemicals for the new rubber industry also, and later became the world leader in rubber chemicals. All the companies ran at capacity to support the war effort. The Kanawha Valley became known as the chemical center of the world, and South Charleston was nicknamed Chemical City.

After World War II, the local industry reached its peak employment by 1950 and then started slowly declining. The chemical industry outgrew the Kanawha Valley. Many of the chemicals produced during the war became commodity chemicals, with demand for production volumes larger than the Kanawha Valley could support. Soon the major corporations were building larger facilities on the Gulf coast and in Texas, where oil and space were plentiful. The Kanawha Valley plants changed to smaller-volume specialty chemicals, plastics, and agricultural chemicals.

Some of the expansion took place within West Virginia. In the 1950s and 1960s, several new plants were built along the Ohio from Huntington to the Northern Panhandle. In 1947, American Cyanamid built a plant near Willow Island on the Ohio River to produce pigments and dyes. In 1954, Monsanto and Bayer built a polyurethane foam plant in New Martinsville. The venture, named Mobay, was later bought out by Bayer. GE and DuPont built new plastics plants in Parkersburg. In the 1960s, Union Carbide built a silicones unit near Sistersville.

As the 20th century ended, the increasingly competitive and globalized chemical industry caused many old companies to shut down or become part of new companies. A Goodyear plant, built in 1959 near Apple Grove to make rubber chemicals, is now called M&G Polymers and makes polyester resins used in beverage and food containers. The Monsanto plant at Nitro became Flexsys, a joint venture of Akzo-Nobel and Solutia. Flexsys closed the plant in 2004, citing foreign competition. Most of the Union Carbide Institute site was sold to a French company, Rhone-Poulenc, in 1986. In 1999, it was sold to Aventis, another European chemical company. Other parts of Carbide's South Charleston and Institute plants were sold to Arco and Lyondell. The Olin Chemical Company in South Charleston became part of Clearon Corporation. The Sistersville silicones plant was bought by an investment group named Crompton. And finally, in 2001, the Dow Chemical Company purchased the entire Union Carbide Company.

As companies merged and old plants were shut down, the number of chemical workers in West Virginia continued to shrink. Much of the reduction over the years reflected the movement of chemical production to areas where materials based on natural gas and oil were more plentiful and cheaper. Advances in technology and computerization also reduced the number of workers required. However, the industry is still a substantial part of West Virginia's economy. In 2009, the industry contributed more than $2.5 billion to West Virginia's annual gross state product. In 2010, the chemical industry employed more than 10,000 workers earning an average of $75,450 per year, the highest among manufacturing sectors in the state.

In 2013, West Virginia's chemical sector included stalwarts such as DuPont, Dow, and Bayer, but the industry in the state is now more diverse. For example, manufacturers operating in West Virginia include the foreign chemical companies Kureha and Braskem, small local companies AC&S and Poca Blending, and start-up companies Aither Chemicals, PolyPlexx, NGInnovations, Liberty Hydro, and SGA Polymers. The availability of cheap and abundant ethane from Marcellus shale and other natural gas fields in the region could lead to a renaissance of sorts in West Virginia's chemical sector over the coming years.