Its southern terminus is near Bloomingburg and Washington Court House at the U.S. Route 62 / SR 3 concurrency and its northern terminus is in Marysville at the intersection of 5th Street and Main Street where the road continues north as SR 31.

When it was designated in 1923 along existing state highways, SR 38 traveled from Ripley on the Ohio River to Marion.

[2][3] This route included its current segment between Washington Court House and Marysville, but also served Russellville and Hillsboro.

[4][5] The route would reach its long-time routing between Washington Court House and Marysville in 1932 when US 62 was brought into Ohio replacing SR 38 between Ripley and Washington Court House.

The old route of SR 38 between Bloomingburg and Washington Court House was turned over to Fayette County.