For more than a millennium before the Columbian voyages, the Ohio River Valley served as one of the great conduits of human civilization in North America. Each of the main prehistoric culture complexes of the central continent was communicated through the Ohio Valley along the region's network of waterways: the Hopewell, Adena, and Mississippian cultures each left its mark in the valley and contributed to a rich and complicated prehistoric legacy. The Ohio Valley emerged then, and has persisted ever since, as a distinctive cultural and economic zone. Influences and contacts flow through the region like blood through the back of a hand; its tributary rivers, united by the great artery of the Ohio River, have always tended to make travel, communication, trade – and conflict – defining features of Ohio Valley communities.

To begin with, there is the landscape. The Ohio River falls from its origins in the Allegheny foothills to the south and west for nearly a thousand miles, fed along the way by nine major rivers and dozens of smaller streams. On its southern bank, the Ohio Valley embraces both the hardscrabble hills of northern West Virginia and the fertile plains of the Kentucky bluegrass, a region marked off by the Alleghenies on the east and the Tennessee River to the south. On the north side of the Ohio the valley is especially accessible through an intricately branching pattern of subsidiary rivers. The big river ties the entire region together at the same time that it divides it in two.