The Ohio River joins the Mississippi River at Cairo, Illinois, creating a major confluence.

At Cairo, Illinois, the Ohio River merges with the Mississippi River, creating an important confluence that significantly impacts the flow of both rivers. The Ohio River drains parts of the Appalachian region and contributes large volumes of water to the Mississippi. This confluence has played a vital role in the region's history, contributing to trade, transportation, and the development of cities along both rivers. It remains a key geographic feature.