Bamberg, Rothenberg odT, or Plan C?

The mobility issues will be challenging in almost any old town center, as you obviously realize. I presume that you will be driving to accommodate your travel. Bamberg is quite hilly. Rothenberg ob Der Tauber is also not very flat. The flattest cool small places I know are Erlangen just north of Nuremberg with a very reasonable downtown with excellent restaurants and beer halls (Ok I used to live there) and Nordlingen which is in a very very flat valley in the center of the Ries Meteorite Crater. The local church is build of meteorite debris welded together with lots of mini-diamonds. Again very historic, not overly touristy, and I always found it comfortable when I visited. Good luck.

A recent bout of cancer seems to have put me permanently behind a walker. I done some thinking about mobility issues.

Bamberg, Würzburg and Rothenburg are all favorites but quite hilly.

Regensburg is our other favorite and it is quite flat. Lots of restaurants and sights. It is a UNESCO World Heritage Site.

The center of Munich is flat, but I can't remember how it's paved. (Which is stupid as many times as I've walked it.) Regensberg is quite flat. The area around Chiemsee is level. Augsberg is pretty flat, but I do remember the cobblestones. Actually Salzburg is flat outside of the Fortress and the ridge across the river. Mannheim is flat. Speyer is flat, but has cobbles. Hope this helps.

Thanks so much for the helpful replies!

After some quick browsing I’m leaning towards a day or two in Regensburg. We might take one day to rest in Frankfurt before heading out, which would reduce my cobblestone adventures to just the single overnight. I hate that it has to be this way—I’d rather take time to appreciate the small towns—but given the circumstances it’s just as well.

I’m now contacting hotels to see about the availability of barrier free rooms, as that’s another challenge. We’ll be content to see the Altstadt briefly and don’t need to stay there, so hopefully that will make things easier.

Google street view has been helpful for investigating the topography of the rest of the trip—Salzburg does appear to have lovely flat sidewalks!—but I was at a loss when it came to some details of the German towns. Thanks again for the help. I would’ve been screwed without it!

Just to throw this in if Regensburg does not work out: The city of Ludwigsburg north of Stuttgart is rather flat and beautiful if I remember correctly, as is Schwetzingen south of Heidelberg - and both are a bit more half way between Munich and Frankfurt. Ludwigsburg seems not to be cobbled, but paved otherwise - it’s been a while, though since I was there last time…

Also, just north of Frankfurt is Bad Homburg, which is a major health and recuperation spa for people with mobility issues. It's not flat, but unless you want to walk from the lower town to the castle it's not steep. Lots of nice parks with smooth paths. I can recommend the Steigenburger Hotel.

If you choose to stay near Stuttgart as suggested, the Mercedes-Benz museum is fantastic (even if you're not that into cars) and accessible.
I am a fan of the thermal pool for recovering from a long flight. The closest spa town to FRA, as far as I know, is Wiesbaden, which is slightly in the wrong direction for you. Also, not super charming. Bad Homburg was suggested. I'm not familiar with that one.

Wiesbaden not charming? It is filled with gorgeous, turn of the century buildings as it was barely bombed in WWII. Beautiful spas there too.
Bad Homburg would be my choice though, whether walking through the Kurpark or checking out the palace of the Kaiser, or visiting the church next door, which is beautiful, art deco style. There are plenty of hotels there.
If you want some more activities, take the bus to the Saalburg Roman fort or to the Hessen Park Open Air museum.
More medieval towns if you can't make it to Rothenburg? Büdingen, Idstein, Seligenstadt, or MIchelstadt. All close by to Frankfurt.

Again, the replies here are so wonderful! This community is delightful.

We’ve decided to spend the first day visiting childhood haunts and stopping at a local winery before heading to Würzburg for the night. That’ll probably just be a hotel on the edge of town for a practical night’s sleep.

The next day we’ll head to Regensburg as recommended. This turned out to be a twist of fate. There is apparently a barrier-free hotel that has an amazing 18 wheelchair-accessible rooms right in Regensburg. For once I won’t have to worry about getting the right room assignment! For all my worrying, I think I’m going to be happy with how this turns out.

From there we’re on to 3 days in Munich, 3 in Salzburg, and 4 in Vienna. So much planning to savor before then! Enjoy your travels, all!

For posterity’s sake, I wanted to add the following info on Regenberg’s accessibility: https://bavaria.travel/stories/citycheck-regensburg-accessible/