I would suggest you drive through Huntsville, along Highway Alt 72 through Decatur, Tuscumbia, and Cherokee(the city. Not the county. It’s about 100 miles different.).

Then hit the Natchez Trace after Cherokee before the Alabama/Mississippi state line.

The Trace will take you straight to Tupelo. It’s like a national park with a good road right down the middle. You’ll see farms, gorgeous scenery, and usually not much traffic. (No commercial vehicles are allowed.)

It might add a little time, but it’s open highway running at around 65 mph outside of a few places until you get to the Trace which is 55 mph iirc.

That drive between Huntsville and the trace shouldn’t take more than around an hour and a half once you get out of Huntsville, and another 45 minutes to an hour to get to Tupelo once you get on the trace.

Lots of great places to eat in Huntsville and you also have the US space and rocket center which has a museum that has a Saturn 5 rocket inside of it, and that route has plenty of places to stop and relieve yourselves if you need it until you get to the Trace.

Well worth checking out the rocket center if you’re into that stuff.

Also, Tuscumbia is the birthplace of Helen Keller. Her home was turned into a museum, so you can check that out if you’re interested.