Appreciate any help with booking a bus ticket from Nuremberg to Prague.

ZOB is not the train station but the main bus station (ZOB = Zentraler Omnibus Bahnhof), which is adjacent to the main train station (Hbf = Hauptbahnhof). There is no other station you could use when arriving by cruise boat. The docks are approx 8km from the train station, a taxi ride takes 15-20 min. Public transport is poor, so I'd assume that your carrier will order a bunch of taxis.

A dummy booking for 15 sep brings up saver fare tickets for €19.90 (bound to a specific bus), flexible fare for 55.10. The German website doesn't bring up a price for first class either but there is a request button. Since the bus includes always seat reservation i wonder if you need a first class (upper deck) seat at all. Unlike the train ride (change of train in Cheb, longer travel time) the bus ride over the autobahn is not that exiciting.

read first class tickets can be exchanged free if needed for a different time - which may make the price difference worth it

All flex price tickets, first and second class, can be exchanged free until the day before departure. There is a hefty exchange fee (€19) for saver fare tickets.

Thank you for your fast and extremely helpful response. The information is appreciated and I feel much more confident in booking the bus. We are really looking forward to our trip!

Last I knew, the bus stop for the bus to Prague was right outside the main entrance to the Hbf in Nürnberg, Haltestelle H on this map. The bus goes non-stop (except for signals) to Prague, there is no other stop in Nürnberg.

I've never ridden that bus, but someone who did said that 1st class in on the lower level, in the front, near the door, while 2nd class is on the upper level, in the back.

When the Bahn says that 1st class fares are not available for the bus, I wonder if they mean that all seats now are 2nd class.

As SLA said, full fare (flexfare) tickets are exchangeable, Saver Fare tickets (2nd or 1st class) are not.

The quickest rail route to Prague is probably the route with a change in Schwandorf, but it is still slower than the bus. However, you can use a less expensive, fully flexible Bayern-Böhmen-Ticket as far as Pilsen.

Update: Maybe the location has changed. The details on the Bahn website show the ZOB as on Käte-Strobel-Straße, which is about 200 yds east of the Hbf, just off Bahnhofstraße. Google Maps shows this location as the Baufinanz-Zentrum and does show bus stops there, but mainly a private bus company, Flex, and some buses to Russia. Maybe the change is too recent for Google to have picked it up. The satellite view on Google Maps shows a lot of taxis in what is supposed to be bus stop 'H'.

The "neighborhood" map (top of this page on Bahnhof.de), does show the Käte-Strobel-Straße location for the ZOB, although it doesn't show the street name.

If you take a taxi from the cruise dock, tell the driver you want to go to the ZOB (tset-oh-bay) or the "busbahnhof".

Maybe the location has changed. The details on the Bahn website show the ZOB as on Käte-Strobel-Straße, which is about 200 yds east of the Hbf, just off Bahnhofstraße.

That's where it always used to be. The Deutsche Touring, another bus company offering buses to Prague, has a map on its web site . Its very easy - just leave the station and keep right and you will see it on the opposite side of the Bahnhofstraße.

BTW -

1. besides the DB and deutsche Touring there are other companies serving the Nuremberg - Prague connection: the ubiquitous Flixbus and two Czech ones. For an overview look up
   busliniensuche.de.

2. If you can find fellow travellers headed to Prague you might consider renting a Czech minivan with driver. There are many companies, e.g. this one, which offers the tranfers for €276. They would pick up you at Nürnberg harbour (if you decide to do that tell the carrier the official adress of the docking station: Europakai 10, Nürnberg (insist on Europakai, not Europaplatz).

The quickest rail route to Prague is probably the route with a change in Schwandorf

Yes, you can catch there the ALEX train originating from Munich, but it will save you just 10 min (total travel time 4:58) against the more scenic northern route via Cheb. Along that route there is a connection every other hour at minute :37 with an easy transfer in Cheb (total travel time is 5:08). You can bring up those connections on the DB web site only by requesting an intermediate stop in Cheb (for the ALEX trains request a stop in Furth im Wald). Prices given on the DB web site are prohibitive, which conforms to their dishonest strategy of luring people into their Prague buses. The trip can be done for a fraction of the price shown. The cheapest offer is the "First Minute Europa" ticket of the Czech Rail, which is available in their web shop; prices start at approx. €14 for the entire trip. And then there are the Bayern-Böhmen-Ticket, which covers you as far as Plzn, combined with a single ticket Plzn-Praha (available online, ridiculously cheap) or the Bayern Ticket, which covers you as far as Cheb, plus a single ticket Cheb - Praha. Total prices for both combinations will be more or less the same.

I don't want to discourage the OP from taking the bus, but personally, I'd prefer the train any time. First, bus schedules are theoretical, the rule of dumb being that long distance trains are some times late and long distance buses sometimes on time. Second, the train route is much nicer than the autobahn - it follows the Pegnitz valley first, then cuts through lonely rural eastern Franconia and after Cheb it meanders through the eastern foothills of the Bohemian forest. The Czech trains of the EC and SC class carry a traditional restaurant car serving draught beer and hearty traditional meals. They have sockets at every seat and WLAN and offer a much more relaxed and comfortable way of travelling than the bus.

You could also search and find 3 or 4 other private bus lines that make the trip for half the price (Flixbus, Goeuro, and Student Agency for example)

We took the Student Agency bus, the bus was great, we were going to Plzen, but the bus went on to Prague.

As I recall, the train was a broken up route that may have been longer or had a wierd connection for us. The bus is not perfect, Traffic can mean the bus is late, not something usually encountered on a train.