The Ohio River is the longest river in the Appalachian region, flowing through several states and forming part of the boundary between the Appalachian Highlands and the Great Plains.

The Ohio River, spanning over 981 miles, is the longest river within the Appalachian region. It flows through or along the borders of several states, including Pennsylvania, Ohio, West Virginia, Kentucky, Indiana, and Illinois. The river plays a vital role in the regional economy, particularly for transportation and trade, and serves as an important tributary to the Mississippi River. It also forms a natural boundary between parts of the Appalachian Highlands and the Great Plains.