one pre-amp with two amps connection.

My pre has two pre-outputs. I am thinking of what if I hook each pre amp out to two different set of amp and different set of speakers. Is it safe to do so? I will of course listen to one amp at a time. What happens to the signal ouput to the amp that I do not turn on? Sounds like the signal output has to go some where, does it flows back into the pre-amp and create an extra load ?
You can do it and it is generally safe or they would not provide two sets of outputs. The only issue is to be sure that the amps have a high input impedance since we cannot know whether the preamp has separate drivers for the two outputs.

The unused output signals are irrelevant.