Its southern terminus is at its interchange with U.S. Route 52 near Felicity and its northern terminus is at its interchange with SR 350 in Clarksville.

On the route of current SR 222 from Chilo to Felicity and its current route between Felicity and Bethel.

[2][3] In 1926 the highway was extended north to Owensville, passing through Williamsburg.

In that same year the route was extended north to Blanchester.

[6][7] On March 9, 1932 the highway was extended north to Clarksville.