Shortly after leaving Fulton, Mississippi, the route joins the Natchez Trace Parkway for 10 miles. After crossing a low divide into Tennessee, the route follows the Tennessee River northward toward its confluence with the Ohio River. This area of western Tennessee and Kentucky is rich in American Indian and Civil War history. The Shiloh National Military Park and the Fort Donelson National Battlefield are points of interest along the way. This also follows The Trace Road through the Land Between the Lakes National Recreation Area, a highway with no commercial traffic. Upon reaching the Ohio River, once known as the dividing line between the slave and free states, the route then heads northeast along the river to end at Owensboro, Kentucky.

More information about this route is available here.