U.S. Route 50 (US 50) runs east–west across the southern part of the state of Ohio, passing through Cincinnati, Chillicothe, and Athens.

The highway passes under Interstate 275 before entering the extreme western suburbs of the greater Cincinnati area.

The road has an at-grade crossing with former Big Four branch line railroad track, before curving southeast.

After the river the route enters Cleves and curves due south and passes through residential properties.

The road parallels the Ohio River and passes through a mix of woodland, residential and industrial properties.

[2][3] US 50 begins a concurrency with SR 264, at an intersection in the Lower Price Hill neighborhood of Cincinnati.

The two routes heads east and is locally known as the Sixth Street Expressway (from Interstate 75 in Queensgate to the Waldvogel Viaduct, which continues to Lower Price Hill).

East of the Mill Creek, the road passes under a railroad track, before an eastbound exit towards Mehring Way.

Fort Washington Way is an eight-lane divided depressed expressway, passing under five city streets.

After the slip ramp the highway curves east, passing over Collins Avenue and having a traffic signal at Torrence Parkway and William Howard Taft Road.

The route enters Fairfax and crosses a few small bridges before an interchange with Red Bank Road.

The route heads through commercial properties as a two-lane undivided highway, passing through Fairfax and into Mariemont.

After leaving the business area of Mariemont the route becomes a four-lane undivided highway, passing through Plainville.

Just before crossing the river, the route passes under an old railroad bridge that now hosts the Little Miami Scenic Trail.

The route curves southeast, before turning northeast, passing through the downtown area of Milford.

[2][3] East of Milford, US 50 becomes a two-lane highway as it travels through Hillsboro and Bainbridge before reaching the outskirts of Chillicothe.

US 50 joins with State Route 32 near the Ohio University Bush Airport–Snyder Field in Albany, west of Athens.

US 50 intersects with U.S. Route 33 east of the city before continuing eastward toward Belpre and the Ohio River.

[citation needed] Prior to August 2007, westbound traffic on Wooster Pike at the intersection between Wooster Pike and Newtown Road did not need to stop, due to a thin concrete barrier and green traffic light arrows pointing up, unless the driver was turning left onto Newtown Road.