The Bluestone River rises from numerous springs on the northwest slope of East River Mountain in Tazewell County, Virginia. The river takes its name from the blue-grey color of the limestone that outcrops along the stream and its banks.

From the mountain, the river flows northeastward to Bluefield, Virginia. This part of the stream follows a generally straight course, with a few meanders. The Bluestone then turns sharply toward the northwest, crossing into West Virginia near Wolfe. In this section, the river cuts through several ridges and has numerous bends. From Wolfe it flows northeastward toward its mouth at New River. There are many more bends along the way, one of which enfolds Bramwell, the old "millionaires' town" built by the coal operators in Mercer County. It is likely that Mary Draper Ingles crossed the Bluestone in her escape from Indian captivity, near its confluence with the New.

The last stretch of the river, from Wolf Creek to its mouth, occupies the scenic Bluestone Gorge. This section had some level land, most now covered by Bluestone Lake. The dam is on New River just downstream from where Bluestone comes in, and it impounds long stretches of both rivers. The villages of Lilly and True were sacrificed for the lake, as was Green Meador's place, once a campground for Union troops in the Civil War. Part of the river is included in Bluestone and Pipestem state parks. The parks are linked by the stretch of river designated as the Bluestone National Scenic River, administered by the National Park Service.

Eades Mill, at the junction of the Bluestone and Camp Creek, was an important gristmill. Bush Creek Falls, on a tributary, was the site of a woolen mill. There was a plan to build a flood control dam at Spanishburg, but it was never constructed. Most of the river is paralleled by roads. The Bluestone Turnpike once connected the New River road with a road at Flat Top, the latter road eventually reaching the Kanawha River by way of Paint Creek. The Bluestone Lumber Company built a railroad, now dismantled, down Brush Creek and along a part of the Bluestone. A hiking trail has been developed along parts of the river.

The total length of the Bluestone River is 86.7 miles. About 55 miles are in West Virginia. The river is slow-running in its upper stretches, with brisker water in the gorge below. The total fall of the Bluestone from source to mouth is 2,125 feet, an average of 24.5 feet per mile. The area of the Bluestone River watershed is 463.53 square miles. West Virginia towns along the river include Coopers, Bramwell, Flipping, Durhing, Montcalm, Rock, and Spanishburg. The major tributaries of Bluestone River are Brush Creek, Little Bluestone River, Camp Creek, Surveyors Branch, and Lorton Lick Creek.