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.