The controversial episode depicted Donald Trump naked in bed with Satan, prompting a White House statement dismissing the show as irrelevant.
Parker also revealed that producers had requested to blur a penis in the episode, a request he rejected.
The premiere additionally targeted Paramount for its recent $16 million settlement with Trump, occurring just after Parker and Matt Stone signed a significant deal with the company.
The episode drew parallels to the cancellation of Stephen Colbert's "Late Show" by CBS/Paramount, which followed Colbert's criticism of Paramount's settlement with Trump.