I am considering driving from Frankfurt down the Romantic Road down to Garmish in one day. Does anyone have an idea on how long that will take and am I better off splitting that up into two days.

Thanks.

Using viamichelin.com and plugging in Rothenburg as a "stopover" from Frankfurt to Garmisch, the route is calculated as 480 km taking an estimated 4-3/4 hrs. This is certainly doable in one day.

I think Michelin misses the mark on this one. From Frankfurt to Garmisch normally takes around 4 hours WITHOUT traffic, plus the speed it pretty much limited to 130km most of the way south of Stuttgart nowdays.
Once your at Munich you need to drive the huge ring road around Munich, and then from there it's another hour or so.
Certainly doable in one day, but expect around 5 hours. Whatever you do be sure and plan your trip to avoid rush hour in Munich.
Also, a stop in Dachau just outside Munich is possible if your interested.

Correction!!! I meant Frankfurt to Munich takes 4 hours.

If you want to drive the actual Romantic Road all the way--the driving time is more like 6 hours for the Romantic Road portion alone. Then you would have to drive from Hohenschwangau to Garmisch another hour or so.

This would be Frankfurt to the start of the RR at Wurzburg, then Weikersheim, Rothenburg, Dinkelsbuhl, Nordlingen, Augsburg, Landsberg, Steingaden/Wies, Fuessen, Hohenschwangau--the designated Romantic Road route; then Hohenschwangau to Garmisch.

As bettyk pointed out, you can also use the Autobahn most of the way getting off at points of interest like Nordlingen or Dinkelsbuhl--this would be somewhat faster.

You wouldn't get involved with the Munich ring road if this is what you had in mind.

But if it is what you intended, then I would make it two days if you wanted to make many stops (e.g., Rothenburg, Nordlingen, Dinkelsbuhl, Oberammergau, etc.) on the way and visit sights like the Wieskirche, Neuschwanstein, Hohenschwangau, and Linderhof, etc.

Listen to Asbachnate and Rufus, they know what tey are talkling about!

I began working on this "section" of our trip after reading this post. We will have been in the Mosel for several days, and will then drive to to Rothenburg ODT. I am thinking about stopping in Schwabisch Hall on the way to our overnight in R'burg. Then driving early after noon to Dinkelsbuhl, Nordlingen, and Landsberg before we stay several nights in Hohenschwangau.

Do you think this sounds like a reasonable way to see these sights, or is it too "full" of an afternoon?