Driving Prague to Amsterdam through Germany

6 days for Frankfurt - Prague - Amsterdam by car?
Makes no sense imo and you will sit too much time in the car compared to exploring.
Try to fly-in to Prague, take train to Dresden or Regensburg and take car from there to drop-off in Aachen or Cologne. Take train to Amsterdam.

Important:
1. Care for driving permission, driving license may not be valid alone.
2. Cross-border rental car is really expensive. Also rental car contract must allow cross-border.

If FRA is fix:
A typical first stop is a day cruise on river Rhine (from Bingen or Rüdesheim) through UNESCO World Heritage Middle Rhine Valley, e. g. a castles tour with KD.

Cologne and Aachen are meaningful but need time to explore.

Thanks for the feedback. Our trip begins in France for a family event then train to Bavaria to meet other family, then Frankfurt w/family. The car allows us to stop and start wherever we chose along the way. We've already reserved it and did confirm we can drive to Prague. The Rhine Valley is something most of the others have already done several times (though not me) so while it's not off the table it does mean a repeat performance for a few of them. We also plan to stop in Rotterdam for an afternoon before landing in Amsterdam.

My understanding is that Czechia is not a "hard" border and in Schengen so crossing is not an issue. We do have our Int'l driver licenses which are acceptable and our rental contract allows for cross borders. Your post prompted me to do a bit of digging and it seems we need a "vignette" to drive in Czechia which is $270. So yes it's more expensive than anticipated but still cheaper than trains for all of us. Thanks for sharing that info, much appreciated.

The info about vignette is correct but it is only 270 CZK.

Info: During Euro 2024 event every border to / from Germany will have intensive security checks (source).

You can identify sights fitting to your filtered interests in this interactive tourist Germany map.

it seems we need a "vignette" to drive in Czechia which is $270.

Well, inflation is racing. But thankfully not so fast. As of today, a 10-day vignette costs around €11 (270 czk). That certainly won't break the bank.

E-vignette Czech Republic. It's only for the Czech Autobahn. No need for secondary streets.
"If you would like to use motorways and certain highways in the Czech Republic, you will need a vignette. The e-vignette is available in the Czech Republic. You no longer have to apply a sticker to your windscreen. Instead you can conveniently get your registration number registered online."
https://www.cze-vignette.com/en/

I'd take the northern route; go up to Rostock and cut across the top of the country. Not a lot of football in those cities and not a lot of tourists either. Well, except Berlin and Dresden. You want to avoid crowds you need to stay away from the Rhine.

Thank you all for the financial lesson of US dollars to CZK lol. I needed that and am breathing a sigh of relief.

Well, turn the car in at Cologne and take the train to Amsterdam to avoid international drop fees.

Thanks Sam. We've already booked the car with drop in Amsterdam. It's primarily paid for with travel points and a small amount of cash. Unless they surprise us with a fee at collection, the contract says it's all inclusive.