The rugged land made the Guyandotte an important route for early settlers. Although the state of Virginia tried to build locks and dams in the 1850s to make it fully navigable, the project failed due to poor construction and was completely destroyed by a major flood in 1861.

However, the river remained vital to the timber industry. When the water was high, daring raftsmen would guide massive "fleets" of logs downriver. This rough-and-tumble commerce ended around 1904 when the railroad arrived, making coal mining the region’s major industry.

The same rapid rises in water that allowed for log rafting caused frequent, devastating flash floods in the valley towns. To protect these communities, the R. D. Bailey Dam and Lake (Wyoming-Mingo line) was built near Justice and dedicated in 1980, helping to control the powerful floods that once plagued the river.