The Ohio River, a major tributary of the Mississippi, flows through parts of the Appalachian region, shaping its geography and history.

The Ohio River, originating from the confluence of the Allegheny and Monongahela Rivers in Pittsburgh, Pennsylvania, traverses several states along the Appalachian region. This river has played a crucial role in the development of the United States, serving as a natural boundary, a route for exploration, and a key waterway for commerce. Its basin is rich in biodiversity and features many tributaries that originate in the Appalachian Mountains. The Ohio River also contributed significantly to westward expansion and remains vital for transportation and recreation. Its scenic landscapes, particularly where it winds through Appalachian foothills, continue to draw visitors and underscore its importance to the region’s ecological and cultural heritage.