Some people say it’s not true:

On March 20, 2006, two days before the episode “The Return of Chef” aired, Roger Friedman of Fox News reported having been told that the March 13 statement was made in Hayes’s name, but not by Hayes himself. He wrote: “Isaac Hayes did not quit South Park. My sources say that someone quit it for him. … Friends in Memphis tell me that Hayes did not issue any statements on his own about South Park. They are mystified.”[29] In a 2016 oral history of South Park in The Hollywood Reporter, Hayes’s son Isaac Hayes III said the decision to leave the show was made by his father’s entourage, all of whom were ardent Scientologists, and that it was made after Hayes suffered a stroke, leaving him vulnerable to outside influence and unable to make such decisions on his own.