KY 104 begins at the Kentucky–Tennessee state line north of Clarksville, where it continues southward as Tennessee State Route 48.

From the state line, KY 104 heads on a northeasterly course to Trenton, where it has a brief concurrency with US 41.

Leaving Trenton, KY 104 continues northeastward to end at its junction with Kentucky Route 181 just south of Elkton.

When Kentucky's state highway system was originally established in 1929, KY 104's current routing was signed as Kentucky Route 181.

KY 104 originally went from a junction with U.S. Route 79 at Guthrie to its current northern terminus.