From the vicinity of present-day White Sulphur Springs the Trail followed Anthony's Creek down to the Greenbrier near the present Pocahontas-Greenbrier County line.

It then ascended the River to the vicinity of Hillsboro and Droop Mountain and made its way through present Pocahontas County by way of future Marlinton, Indian Draft Run, and Edray.

The first permanent white settlers west of the Alleghenies have traditionally been considered to have been two New Englanders: Jacob Marlin and Stephen Sewell, who arrived in the Greenbrier Valley in 1749.

They built a cabin together at what would become Marlinton, but after disputing over religion, Sewell moved into a nearby hollowed-out sycamore tree.

They may well have been the first to settle what was then called the "western waters" — i.e., in the regions where streams flowed westward to the Gulf of Mexico rather than eastward to the Atlantic.

At the age of twenty, Stuart was a member of the 1769 survey by citizens of Augusta County, Virginia, which explored the wilderness of the Greenbrier Valley to the west in preparation for European settlement.

In 1774, he led a company of Greenbrier troops in the Battle of Point Pleasant at the confluence of the Kanawha and Ohio Rivers.

Over three-fourths of the watershed is an extensive karstic (cavern system), which supports fine trout fishing, cave exploration and recreation.

It is impossible to tell how large a cave system is by looking at the surface, and developers often build their structures too close to the open spaces beneath the ground.

Bones discovered by saltpeter miners in Haynes Cave close to the river in Monroe County were sent to (future President) Thomas Jefferson, who identified them as a previously unknown species.

The West Virginia Department of Environmental Protection and various concerned citizen groups are working to prevent further stresses upon the river.