The episode, called My Big Fat Geek Wedding (a joke on the real film from last year called My Big Fat Greek Wedding), shows Principal Skinner changing his mind about his marriage to Edna.
He gets what is called "cold feet", and Edna calls the marriage off. She then has a crush on "Comic Book Guy" at the convention.
Groening has appeared on the show before - but only in a framed photo on the wall of Comic Book Guy's shop.
This will be his first speaking part.
The Simpsons is now in its 16th series in the US.