Seems that way. Trey and Matt have feinted change before, but things have never aligned this neatly before. They had a big 200 episode where they basically referenced every celebrity parody they've ever made, this alone would signify that they're aware that the show has had a long run.
During that episode, they elected to harp on one of their favorite subjects, censorship, only to, for only the second time, have their work censored, and taken off the air for the first time.
This would be undoubtedly depressing, as if everything you've ever tried to express in your artwork has fallen on deaf ears.
The episodes from this point on noticeably declined, with few exceptional pieces, even the funny one's were often lacking in the strong themes or overarching and controversial messages of episodes gone by.
Season 15's first episode was sub par at best, Matt and Trey have been known to place importance on their season openings and closings, the fact that this episode relied so heavily on shock value, and was so mercilessly drawn out was a sign of stagnation, especially with an idea as fertile as accidental contract obligation.
Episode 7 of Season 15 is the only episode in the history of South Park(To my knowledge) to end on such a serious and depressing note, there have been changes, there have been downers, but at every turn, even dealing with real world tragedy, like the death of Chief/Isaac Hayes, South Park has always played itself for laughs.
There was noting funny about the ending of last weeks episode, and this time, that was the intention.
South Park is one of my favorite shows to ever air on Television, and even I can feel the passion dying, but the ending of Episode 7 felt genuine, the passion was there, and maybe that passion was born of the need to move on, but I'd rather South Park die with the dignity and honesty it's prided itself on all these years, then press on and become mechanical and hollow inside.
It's been great, but I think this is the end, it's time to let go.