I've tried to find better routes to Nashville/Smokey mountain area, but it's pretty bleak until you get to Kentucky. We tried the "scenic" route around Chicago and it was a nightmare - constant traffic and slow going through suburbs and towns. You have to be well outside of Chicago to avoid that - as in Rockford.

Best I could do was US 41 to Evansville IN then over. It's still mostly 4 lane, but not quite as ugly as I-65.

 

That's probably the best option. I've ridden 41 from here (central Indiana) both directions. I've been all the way to Wisconsin and then all the way to the front gate of Fort Campbell, KY. going the opposite direction. On the north section, 41 goes through Chicago on Lake Shore Dr. and then through Stoney Island. If you hit that section at the wrong time of day, it can be brutal due to traffic. Other times it's decent because of the scenery around the Lake. Stoney Island is mostly a ghetto of course. Somewhere around Carbondale, IN (going south), you want to cut off on IN 63. It is a 4 lane highway that turns back into US 41 around Terre Haute, IN. If you stay on 41 in that section, it turns to two lanes and is quite curvy. It's fun, but usually very slow due to small towns and state parks north of Terre Haute. If memory serves, 41 turns into 150 from Terre Haute south towards Vincennes, IN.

I think you could stay on 150 all the way to southern KY. You may have to run US 75 to Knoxville from the terminus of 150. That route would take a long time to get you to the Smokies, but if you have the time, it would probably be fun.

 

Unless it was 6AM on a Sunday morning I would avoid street riding in Chicago. I've done it many times at other times of the day but I know it pretty well and where, and where not, to be at a given time of day. Typically I'll just take 294 around and get it over with. Only once was I stuck in a traffic jam (and boy did it suck) on 294 on a bike. It was a friday afternoon with construction lane closures. Otherwise the biggest issue is speed. You need to be comfortable running 80 bumper to bumper or get run over.

We rode down 120 to Lake Geneva and then 47 farther south last time. On the map it looks promising. But in reality it's a nightmare. We left in the afternoon and the goal was to make Indianapolis by nightfall - normally 4.5-5 hours for us. Because of the shortcut we made it to Maryville - normally 2.5 hours. The shortcut cost me 2-2.5 hours vs the toll roads.

I like that spot that's 2 lane. If we're breaking the trip up, like staying in Evansville, we'll take it as it could add as much as 15 minutes. But if we want to make Nashville, we'll usually we'll just stay on the 4 lane as mentioned above and then run straight down finishing up on I-24.

Another option to avoid Indiana altogether, and by default, Chicago, is to run 51 down the middle of Illinois to Carbondale. I've done this and it's time consuming, but mostly 2 lane. Lots of towns. The payoff begins when you get near Carbondale. Basically take any squiggly road towards Land Between the Lakes, pick up 49 and run that down to Tennessee. It's a parkway, so fairly scenic. 49 south of the parkway is very nice. Take that to 46, and them into Nashville on 70. We stay at the Holiday Inn Express on Hwy 70 in West Nashville. Relatively cheap compared to points east of there.

All of the above is our approach through Nashville. Sometimes to hit the Smokies we will go in through Cincinnati. Again, no great routes to Cincinnati that I am aware of. Sure, there's some two lane that is okay, but we like to just get Indiana over with. The great riding starts in Kentucky and boy, it is some very good riding.

 

Take the super slab to Cincinnati, from there you can grab any number of of back roads and head south into KY. state route 42 out of Ohio and through Ky is a great ride which will eventually dump you off on 31w which will take you all the way to Nashville. If your heading to the pigeon forge area there are other back roads that will get you west in Ky.. As others have said Ky has some really nice riding.

From Milwaukee to south of Chicago I would take the highway no matter what. Once south of there Id say you can grab a number of back roads to get through Indy.

Enjoy your trip, We just came from Cincinnati to Milwaukee last year, we also did a Nashville trip and pigeon forge trip. Heading south had the better riding for sure.

 

Once in the Chicago area you could ride the Lincoln Highway (looks like the 'old road' intersects downtown somewhere) into central Ohio. Farther east than where you would head south it rolls through Canton on its way to Pittsburgh. That would give an opportunity to ride through southeast Ohio which is hilly and beautiful before getting into the foothills of eastern Kentucky or western West Virginia.