William B. Wilson was born in the Scottish village of Blantyre on April 2, 1862. His family then emigrated to the village of Arnot, Pennsylvania. After attending local schools, Wilson dropped out to work in the coal mines, where he would remain until 1898. Wilson was president of the district miners' union of the National Progressive Union from 1888 to 1890, earning a reputation as a fervent unionist, an honest broker, and a dedicated worker.

Wilson ran unsuccessful political campaigns for the Pennsylvania state legislature in 1888 and the U.S. House of Representatives in 1892. In 1900, however, he won election to serve as secretary-treasurer for the United Mine Workers of America (UMWA), where he would stay until 1908.

As a Democrat, Wilson would also win a seat in the U.S. House of Representatives (1906), serving a staunchly Republican district. He would be known as labor's best friend during his time in the House (1907-1913), where he was chairman of the Committee on Labor, the Committee on Mines, and the Committee on Merchant Marine and Fisheries.

After President William Howard Taft separated the Department of Commerce and Labor into two separate agencies on his last day in office, President Woodrow Wilson named William Wilson to head the newly formed Department of Labor, despite it having no permanent building. Wilson was, in some ways, the ideal candidate for the position, for he was the author of legislation separating the two cabinet agencies. The new department would consist of four bureaus: the Bureau of Labor Statistics, the Bureau of Immigration, the Bureau of Naturalization, and the Children's Bureau.

Wilson remained in the cabinet from 1913 to 1921. Thereafter, he ran unsuccessfully for the U.S. Senate in 1926 while at the same time pursuing agricultural and mining interests. William Wilson died at his home in Blossburg, Pennsylvania, on May 25, 1934.