Plan with Rovo. Drive with your favorite map.
St. Louis to Nashville covers about 305 miles and just under 5 hours, and unlike most routes into Nashville, it isn't a single interstate — you'll link I-64 East, I-57 South, and I-24 East in sequence.
The route leaves St. Louis on I-64 East, picks up I-57 South through southern Illinois, then crosses the Ohio River into Kentucky where it becomes I-24 East, running through Paducah and Clarksville before reaching Nashville. It's a bit more of a patchwork than a route like Louisville-to-Nashville, but the interstate changes are well-marked and there's no backtracking involved.
The three-interstate handoff sounds more complicated than it drives — each transition is a clean interstate-to-interstate exit, not a surface-street detour. Southern Illinois and western Kentucky are sparser than the Tennessee end of the trip, so it's worth topping off fuel in Marion or Paducah rather than waiting until you're deep into the drive.
Plan This Route with Rovo →No. I-64, I-57, and I-24 are all toll-free for this entire route — there's nothing to budget for in tolls.
I-57 South through southern Illinois is the most direct interstate link down to I-24, which then carries you into western Kentucky and Tennessee. There's no interstate that cuts a straighter diagonal line, so this three-highway combination ends up being both the fastest and simplest option.
Yes — at just under 5 hours of driving, most people do this route as a single day, though it's long enough that a stop in Marion or Paducah for a real break is worth building in rather than pushing straight through.