Kentucky Fried Chicken is a real fast food chain restaurant famous for its fried Chicken. It is also one of the favored fast food places of the boys and it was first seen in "The Death of Eric Cartman".
In "The Death of Eric Cartman", the boys wait anxiously for Sharon Marsh to bring home KFC after her grocery shopping. Before they are allowed to eat however, she requires them to help her unload the car. Cartman urges the other boys to unload the car, saying that it will go faster that way. As Stan, Kyle and Kenny do so, Cartman eats the skin off of every piece of chicken ("the best part" of it) and leaves the chicken itself behind. The boys are left devastated (Kenny crying) while Cartman goes home, unconcerned about ruining dinner for the others. After Cartman has a hard night of crapping on the toilet, he is convinced that the chicken killed him (it actually broke the toilet).
In "The F Word", the boys grow sick and tired of Harley Riders in South Park so plot assorted ways to get them to realize that no one likes them or thinks they're cool. Cartman's plan is to eat several buckets of KFC, then use the food to help him crap on their motorcycles, then add little flags calling them "Fags".
In "Medicinal Fried Chicken", the only KFC in South Park is closed down, along with all the other KFCs in Colorado, to make room for a Medical Marijuana Dispensary. This causes Cartman (who is going through withdrawal of KFC) to work for Billy Miller who, along with Colonel Sanders, is moving illegal shipments of KFC into the state. Cartman later overthrows Billy, but when he fails to follow Colonel Sander's orders, a hit is taken out on him. KFC is later allowed to re-open, when it is believed that KFC was a medicinal compound that stopped testicular cancer. It was also mentioned in "Insheeption".
In "Ass Burgers", KFC led a battle with other fast food chains against Cartman's burger stand; the others being McDonald's, Pizza Hut, Taco Bell and Chic-fil-A. During the melee the Secret Society of Cynics fight in to stop the restaurant owners' assault, on the pretense of them being the cause of the worlds problems. The Cynics destroy themselves during the fight and the Cartman Burger patrons learn the disgusting truth about about how the burgers are made, causing an end to the endeavor.