The Williams River rises in Pocahontas County at an elevation of almost 4,000 feet. From its source it flows 33 miles to Cowen, where it enters the Gauley River. The Williams River watershed takes in about 132 square miles of Pocahontas and Webster counties. The major tributary of the Williams is the Middle Fork, which has its source at more than 4,300 feet elevation, also in Pocahontas County.

The origin of the river's name is not certain. According to one account, it comes from William Ewing, a Revolutionary War veteran, who lived near Buckeye in Pocahontas County and is supposed to have owned land on the river's headwaters.

The remote and rugged watershed was never heavily populated. Two families who settled near the headwaters of the river in 1847 soon found the isolation overwhelming and left "Dutch Bottom" for more settled parts of Pocahontas County. One of the families, the Stultings, moved to Hillsboro, where their most noted descendant, author Pearl S. Buck, was born in 1892. The Hammons family settled on the river before the Civil War, and in the 1960s and 1970s family members became well known due to their knowledge of traditional music.

Two resources in the Williams watershed, timber and coal, were developed. In the post-Civil War period, the timber in the watershed came to the attention of lumbermen. In the 1890s, logs were floated down the river in the flood tides of spring to a mill at Camden-on-Gauley. Most of the timber in the Williams watershed was taken out by log train from 1905 to about 1940, to mills at Marlinton and Richwood. Coal mining activity continued on the lower Williams into the 1970s.

The isolation and ruggedness that hindered the settlement of the watershed allowed most of it to return to a near original state following the timbering, and today perhaps its most important value is for recreation. The land owned by the lumber companies went to the federal government to be included in the Monongahela National Forest, with part of the Williams River watershed now in the Cranberry Wilderness Area. For generations the river has been a popular fishing stream, and it is regarded as one of the top five trout streams in the state. It is one of the "big three" (the Cranberry, Williams, and headwaters of the Elk) that can be fished together.