At the intersection, westbound US 250, which had been heading north–northwest, turns to the west while its roadway continues as SR 21.

The route next proceeds north into the city of Massillon, becoming a four lane controlled access highway at an interchange with US 30 and takes Interstate 77 Alternate status from it.

SR 21 merges onto I-77 (exit 136) in Copley Township west of Akron, dropping the assignment of Interstate 77 alternate.

It then passes through Brecksville and into Independence, where it crosses Interstate 480 on an overpass immediately east of I-480's interchange with I-77.

While I-77 directly serves the larger cities of Canton, Akron and Cleveland, SR 21 connects the smaller communities of Massillon and Norton (and indirectly Barberton), and serves some Akron and Cleveland suburbs as a local through route.

Very heavily traveled before the Interstate era, much of SR 21 is divided highway or even freeway.