US 50 enters Ohio from
Indiana at a traffic light with State Line Road. The route heads northeast as a four-lane undivided highway, passing through farmland and paralleling the tracks of the former
Baltimore and Ohio and
Big Four Railroad tracks. 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. US 50 has a traffic signal at the intersection with
SR 128. Southeast of SR 128, US 50 becomes a four-lane divided highway and crosses over the
Great Miami River. After the river the route enters
Cleves and curves due south and passes through residential properties. In Cleves the highway has a traffic signal with
SR 264, before leaving Cleves and entering
North Bend. In North Bend the road continues to pass through woodland and residential properties, before passing the monument and tomb of President
William Henry Harrison. The highway curves east-southeast and becomes a four-lane undivided highway, before leaving North Bend. The road parallels the
Ohio River and passes through a mix of woodland, residential and industrial properties. The route begins to curve northeast and enters Cincinnati. 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). The expressway heads east as a six-lane divided highway passing through industrial properties. As the highway heads east it crosses over a railroad track and the
Mill Creek. East of the Mill Creek, the road passes under a railroad track, before an eastbound exit towards Mehring Way. Followed by a westbound entrance from Harriet Street, before passing under another railroad track. The highway has an interchange with Freeman Avenue, this interchange does not have a westbound exit. The expressway passes over some railroad tracks and Linn Street, followed by an eastbound entrance and westbound exit to and from Linn Street. East of the interchange with Linn Street, is a bridge over Gest Street, with a westbound exit. After Gest Street, is an interchange with SR 264, this interchange serves downtown Cincinnati. The Sixth Street Expressway ends at an interchange with
Interstate 75 (I–75) and Second Street. US 50 curves southeast and begins a concurrency with
I–71. I–71 and US 50 head east through downtown on an expressway locally known as
Fort Washington Way. Fort Washington Way is an eight-lane divided depressed expressway, passing under five city streets. The highway passes
Paul Brown Stadium and
Great American Ballpark, before I–71 leaves US 50. East of I–71, US 50 is locally known as Columbia Parkway, a four-lane divided highway. The parkway curves northeast having an interchange with
I–471, on the east side of downtown. After I–71 the route passes through residential areas, parallel to the Ohio River. The road has an eastbound exit and a westbound entrance interchange with Martin Drive. After Martin Drive the roadway passes through woodland areas as a six-lane undivided highway. The parkway has an eastbound
slip ramp with
U.S. Route 50 Truck, east of this ramp trucks are not allowed. 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. East of the traffic signal the route curves southeast having a traffic signal at Delta Avenue. East of Delta Avenue, the roadway becomes a four-lane undivided highway, having a traffic signal at Stanley Avenue. The route becomes a four-lane divided highway, before making a very sharp northeast. After the sharp curve US 50 heads northeast, having an interchange at
SR 32,
SR 125, and
SR 561, the street is locally known as Beechmont Avenue. Northeast of Beechmont Avenue the parkway crosses over both Linwood Avenue and Heekin Avenue, before an interchange with Eastern Avenue. The Eastern Avenue interchange only allows for westbound exit and eastbound entrance, it is also the eastern terminus of US 50 Truck. From this interchange east truck are allowed. The route enters
Fairfax and crosses a few small bridges before an interchange with Red Bank Road. The highway passes through commercial properties having a traffic signal at Wooster Pike. The traffic signal at Wooster Pike is the eastern terminus of the Columbia Parkway. US 50 heads northeast, locally known as Wooster Pike. The route heads through commercial properties as a two-lane undivided highway, passing through Fairfax and into
Mariemont. In Mariemont US 50 becomes a two-lane divided highway passing through residential properties. The roadway becomes a four-lane divided highway in the business area of Mariemont. After leaving the business area of Mariemont the route becomes a four-lane undivided highway, passing through
Plainville. The route becomes a two-lane highway with a
center turn lane, at an intersection with Newtown Road. The road curves northeast, passing north of the
Kroger Hills State Reserve The highway enters
Terrace Park, having an intersection with
SR 126, this intersection is also the western terminus of
SR 28. Just before crossing the river, the route passes under an old railroad bridge that now hosts the
Little Miami Scenic Trail. Both US 50 and SR 28 cross over the
Little Miami River and enters the City of
Milford. The route curves southeast, before turning northeast, passing through the downtown area of Milford. North of downtown the roadway curves east, passing through residential properties, with some commercial properties. The concurrency turns northeast and has a six-way intersection, where US 50 turns southeast and SR 28 continues northeast. US 50 heads southeast as a four-lane undivided highway, passing through commercial properties. The highway has a traffic signal at
SR 131 and
Milford Parkway, Milford Parkway gives access to I–275. Southeast of this intersection the roadway narrows to a two-lane divided highway. The highway passes under I–275, with no access. The route curves due south and has an intersection with
SR 450 (Milford Parkway), SR 450 has access to I–275. during its brief concurrency with U.S. Route 50 and
Ohio State Route 32 in
Athens. East of Milford, US 50 becomes a two-lane highway as it travels through
Hillsboro and
Bainbridge before reaching the outskirts of
Chillicothe. In Chillicothe, US 50 becomes Western Avenue and then Main Street before merging with
U.S. Route 23 and
U.S. Route 35 east of the city.
State Route 104 overlaps US 50 through downtown Chillicothe. As US 50 leaves Chillicothe it becomes a two-lane highway once again as it winds its way through
McArthur and heavy forested
Southern Ohio before reaching the outskirts of
Athens where it becomes a four-lane highway. It remains four-lane until reaching the Ohio River. 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. US 50 begins to overlap SR 7 near
Reedsville as it heads north along the river, and splits from SR 7 before it crosses the river on the
Blennerhassett Island Bridge to Parkersburg, West Virginia. ==History==