I plug in my Harmon-Karmon JBL Creatures (line-out, not USB) and they immediately cutoff the Mac speakers.
But those circuits are right next to each other in the case, easy matter to do that. USB is another matter.
I have read where both work (Mac speakers & USB speakers), however, the speaker controls do not control the USB speakers.
So you cannot use the keyboard to mute them, for example.