It joins US 41 on the southeast side of Hopkinsville before that route's interchange with the Pennyrile Parkway (officially designated as I-169).

After its junction with KY 800, it traverses the Pennyrile State Forest; the junction with KY 398 provides access to the Pennyrile Forest State Resort Park.

KY 109 traverses more forested areas before entering Hopkins County.

At Dawson Springs, KY 109 has junctions with US 62, where it has a brief concurrency before branching off to traverse an interchange with I-69 (formerly the Western Kentucky Parkway) before exiting the town.

It continues northwestward into Union County; at Sturgis, it begins a concurrency with U.S. Route 60 (US 60) for a few miles.