The eastern terminus is at PA 88 in the Jefferson Township community of Dry Tavern.
The route turns east and intersects PA 221, passing Greene County Memorial Park before continuing into wooded areas.
The road crosses the Norfolk Southern railroad line and the South Fork Tenmile Creek into Jefferson Township before turning northeast again and entering the borough of Jefferson.
In this borough, PA 188 passes a mix of homes and businesses.
Upon crossing back into Jefferson Township, the route winds east through farms and forests with a few residences.