The pair appeared alongside executive producers Rob Lazebnik and Matt Warburton and supervising producer Mike Anderson to tease details of the Fox comedy's future at the San Diego convention.
The team confirmed that celebrities such as Joan Rivers, Andy Garcia and author Neil Gaiman will lend their vocals to episodes airing in the US from September 25.
Jean also spoke of Glee star Jane Lynch's appearance in an episode entitled 'Replaceable You' and confirmed that Kiefer Sutherland will make his second Simpsons guest appearance following his cameo in season 18's 24 parody '24 Minutes'.
The team further said that the show's iconic Halloween special will air on October 30, with the 500th episode scheduled for February 19.
They also teased a time-travelling Christmas episode and a "format changer" that reveals the history of Moe's Tavern, to which Jeremy Irons will lend his voice.
Jean and Groening confessed during the panel that they often struggle to come up with fresh ideas after two decades on air, but are already considering plots for the show's final season - including one which plays with the Simpson family's previously static ages.
Jean said: "It's never easy. The hardest thing after 500 episodes is thinking of new ideas. We sit around the room going 'did that, did that'. It's not easy and we take it very seriously."
Groening added: "We may [age the characters] when we run out of ideas. That may be the last sad season. Bart will turn 11."
Other stars previously scheduled for a Simpsons guest spot include Michael Cera and Social Network actor Armie Hammer.
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