Nick: Nothing really serious along the route. Shortest would be to pick up I-26N at Spartanburg, NC- there's a 2 mile climb at 7% near Hendersonville, NC. Pick up I-40W at Asheville. Most of the grades and curves through the Smokies are fairly mild. At Knoxville, on I-75N there is a 5-6% climb over 4-5 miles near Jellico. (Almost at the Kentucky border) Nothing significant after that, use I-64 or 74 to get over to I-65 then on to Chicago....
It's a beautiful area to drive through, should be pretty in the spring.
I been though there both directions, no challenge for my 36ft DP with Cummins 260 hp ISB, and toad.
If concerned about a particular area, look at Google Maps satellite view and street view.......
Hooligan, Pensacola, Fl -U.S. Coast Guard 1956-1985
2016 Thor Siesta Sprinter 24ST diesel
Our Pug "Lily" & "George" the Newfoundland