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The Ohio River Scenic Byway in Ohio is a 452-mile (727-km) stretch of the 943-mile (1518-km) Ohio River Scenic Byway. The route in Ohio stretches from the Indiana state line near Cincinnati to its western terminus at the Pennsylvania state line in East Liverpool, Ohio. The route follows the Ohio River for most its length and is largely concurrent with sections of U.S. Route 50, U.S. Route 52, and Ohio State Route 7. The route continues eastward through Indiana and Illinois to its western terminus at the confluence of the Ohio River and the Mississippi River in Cairo, Illinois. The route passes through multiple cities along the Ohio River, including Cincinnati, Portsmouth, and Marietta, before terminating in East Liverpool.

The byway is divided into four regions within the Ohio section: West, Central, Southeast, and East. The West Region covers Hamilton, Clermont, and Brown counties. The Central Region covers Adams, Scioto, and Lawrence counties. The Southeast Region covers Gallia, Meigs, Athens, and Washington counties, while the East Region covers Monroe, Belmont, Jefferson, and Columbiana counties.

Many historical sites are present along the route, including the birthplace of U.S. President Ulysses S. Grant in Point Pleasant, Ohio. Also present along the route is Ripley, Ohio, an important city along the Underground Railroad. The route also passes through Shawnee State Forest and Wayne National Forest

The Ohio River Scenic Byway is designated as an Ohio Scenic Byway and was designated as a National Scenic Byway in 1998 alongside Illinois's section by the Federal Highway Administration, part of the U.S. Department of Transportation. Indiana's section was designated in 1996.

Route Description

 * Western Terminus: at the Indiana state line
 * in Cincinnati
 * in Proctorville
 * Meigs County Road 21 in Middleport
 * north of Middleport
 * east of Pomeroy
 * at Torch
 * at US 30 in East Liverpool
 * Eastern Terminus: at the Pennsylvania state line