In 1830, the Louisville and Portland Canal (now the McAlpine Locks and Dam) bypassed the rapids, allowing even larger commercial and modern navigation from the Forks of the Ohio at Pittsburgh to the Port of New Orleans at the mouth of the Mississippi on the Gulf of Mexico. The lower Ohio River just below Louisville was obstructed by rapids known as the Falls of the Ohio where the elevation falls 26 feet (7.9 m) in 2 miles (3.2 km) restricting larger commercial navigation, although in the 18th and early 19th century its three deepest channels could be traversed by a wide variety of craft then in use.

The river became a primary transportation route for pioneers during the westward expansion of the early U.S. It is the source of drinking water for five million people. Through its largest tributary, the Tennessee River, the basin includes several states of the southeastern U.S. The river flows through or along the border of six states, and its drainage basin includes parts of 14 states. It is also the 6th oldest river on the North American continent. It is the third largest river by discharge volume in the United States and the largest tributary by volume of the north-south flowing Mississippi River, which divides the eastern from western United States. It is located at the boundary of the Midwestern and Southern United States, flowing in a southwesterly direction from western Pennsylvania to its mouth on the Mississippi River at the southern tip of Illinois. The Ohio River is a 981-mile (1,579 km) long river in the United States. Little Kanawha River, Kanawha River, Guyandotte River, Big Sandy River, Little Sandy River, Licking River, Kentucky River, Salt River, Green River, Cumberland River, Tennessee Riverīeaver River, Little Muskingum River, Muskingum River, Little Hocking River, Hocking River, Shade River, Scioto River, Little Miami River, Great Miami River, Wabash River

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