The route forms a broad southern arc that passes through the rural Middle Tennessee towns of Dover, Erin, Charlotte, Ashland City, Pleasant View, and Springfield.

[2][3][4][5][6] SR 49 begins in Stewart County in downtown Dover at a junction with US 79/SR 76 as a primary highway.

It goes east, paralleling the Cumberland River before turning south and having an intersection with SR 233.

It then goes through some more hills and farmland, having an intersection and concurrency with SR 46 before crossing into Dickson County.

SR 49 then enters Pleasant View and intersects US 41A/SR 112 before having an interchange with I-24 and crossing into Robertson County.

[8] Until the 2000s, SR 49 extended north on The Trace Road to the Kentucky border.