The industrialization of West Virginia during the late 19th and early 20th centuries attracted enormous capital into the state's railroads, timber, coal, and other industries. Industrialization dramatically altered the size and composition of the population. West Virginia's southern coalfield population nearly quintupled between 1880 and 1920, from 93,000 to 446,000. In the new coal company towns, native Whites, Blacks, and some 25 different nationalities converged in a bewildering array of cultures. Nevertheless, the miners soon came to focus on their common economic interests, and to improve their bargaining position through union organizing.

The effort to establish the miners' union, and the operators' resistance, played a major role in shaping the history of West Virginia in the 20th century. The United Mine Workers of America made little progress during the first decade of the century, although the octogenarian labor organizer Mary Harris "Mother" Jones had sporadic success in the Kanawha Valley. UMWA President John Mitchell came to Charleston in 1907 to launch a major union offensive, only to be defeated by injunctions and company guards.

For their magnitude and level of violence, several struggles for union recognition have entered the realm of legend: the Paint Creek-Cabin Creek mine war of 1912—13; the Mingo mine wars of 1919—21; and the March on Logan in 1921. The march involved at least 10,000 people and entailed episodes that have become infamous in their own right, including the Battle of Blair Mountain, the Matewan Massacre, the assassination of Matewan police chief Sid Hatfield by company agents, and the treason trials.

Although violent strikes in the coal industry are an important theme in the history of organized labor, other strikes in West Virginia achieved national prominence as well. One of the most important, the national railroad strike of 1877, began on the Baltimore & Ohio Railroad at Martinsburg and brought transportation to a standstill throughout most of the eastern United States.

When U.S. District Judge Alston G. Dayton decided with the Hitchman Coal and Coke Company in 1907 that union organizers were violating the federal anti-trust laws, and allowed an injunction to stop them, he handed companies a powerful weapon for their war against organized labor. With the government on their side, the companies crushed the union movement, and the period of the 1920s was the low point for organized labor in the Mountain State.

Although the early struggles failed, they nevertheless produced numerous indigenous leaders, some with national recognition, such as Frank Keeney, Fred Mooney, and Bill Blizzard. Much later, Arnold Miller, a miner from Cabin Creek who led the reformist Miners for Democracy, ousted Tony Boyle as president of the UMWA in 1972. Still later, in 1995, another miner from Cabin Creek, Cecil Roberts, became president of the UMWA. There were others too, such as Wheeling born Victor and Walter Reuther, both of whom became officials of the United Autoworkers. Walter became president of the UAW and played an important role in the CIO and the civil rights movement.

Business and government repression during the 1920s prepared the ground for a triumphal return of organized labor with the election of President Franklin D. Roosevelt in 1932. The National Industrial Recovery Act in 1933, particularly Section 7a, which guaranteed workers the right to collective bargaining and outlawed yellow-dog contracts, was hailed as labor's Magna Carta. The act was declared unconstitutional in 1935, but by then most of the industrial workers in West Virginia had been unionized. Quick passage of the Wagner Act that same year preserved labor's right to collective bargaining.

Some unions had seemed to be headed for extinction, but Roosevelt's New Deal gave them new life. West Virginia's glass workers are a case in point. By the 1930s, the tri-state upper Ohio River region had more than half of the glass factories in the nation. These factories specialized in bottles, window glass, or tableware. By the 1880s, glass workers were organized into three strong craft unions based on these specializations. The glass workers' unions were dominated by French, Belgian, and German immigrants who passed the craft on to their sons. Their tight control of production provided strong incentive for glass companies to mechanize their plants in the early 20th century. The unions fought bitter strikes but failed to deflect the introduction of technology by the 1920s. Legislation protecting the right to organize unions during the 1930s revived the glass workers' organizations and boosted union membership among West Virginia's 13,000 glass workers.

UMWA President John L. Lewis challenged the American Federation of Labor in 1935 by initiating a campaign to organize workers by industry rather than along craft lines. The resistance of the AFL resulted in the creation of a federation of industrial unions, the Congress of Industrial Organizations. When the West Virginia Federation of Labor refused to expel unions that also belonged to the CIO, the national AFL revoked the federation's charter. In 1937, the state labor federation was accepted into the CIO's new state organization. Later, most West Virginia unions participated in the merger of American unions into the AFLCIO.

Although the newly formed Steel Workers Organizing Committee (United Steelworkers of America) successfully organized most of the American steel industry in the late 1930s, the group failed in its protracted campaign to displace the Employees Security League, a company union at Weirton Steel. When the National Labor Relations Board recognized the Security League as the legitimate bargaining agent for Weirton employees in 1950, it became the largest independent union in the steel industry. It survives today as the Independent Steelworkers Union.

Chemical industry giants, such as DuPont, also attempted to retain the loyalty of their employees in West Virginia through employee representation plans. Chemical companies practiced "welfare capitalism," or company paternalism, to engender loyalty among employees and their families by organizing recreational leagues, publishing newsletters, hosting company picnics, and favoring the relatives of current workers when hiring new employees. Nevertheless, these efforts did not prevent the labor movement from trying to organize the chemical workers, and between the 1930s and 1960s, the United Mine Workers District 50, the International Association of Machinists, and the Oil, Chemical and Atomic Workers competed to unionize these plants. Since the 1960s, those chemical workers who were union members belonged to either the International Chemical Workers Union (AFL) or the Oil, Chemical and Atomic Workers Union (CIO).

Labor and capital relations became relatively stable during and after World War II. The restructuring of the post-war economy, however, posed a threat to organized labor that was most evident in the coal industry. Machinery began to replace miners during the late 1940s and continued unabated at the turn of the 21st century. The number of miners declined from 127,304 in 1950 to 59,098 in 1960, and by 1999 only about 20,000 miners remained in West Virginia. Similar processes were at work in the other basic industries. The net result has been fewer jobs and an out-migration of West Virginians to other states. The dramatic decline of employment in the heavily unionized basic industries, and the rapid rise in the non-unionized service sector, have produced a sharp decline in organized labor in West Virginia.