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 cross 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.