The Simpsons are set to meet the Griffins in a crossover episode of Family Guy next year.
Fox announced the two families would meet in an episode titled The Simpsons Guy, where the Griffins take a road trip and end up in Springfield.
Simpsons voice actors Dan Castellaneta, Julie Kavner, Nancy Cartwright, Yeardley Smith and Hank Azaria will all guest-star in the instalment.
The show is scheduled to be broadcast in the US next autumn.
Fox said the episode will see the Griffins "greeted by a friendly stranger named Homer Simpson who welcomes his new 'albino' friends with open arms".
The families become fast friends with Stewie becoming obsessed with Bart and his pranks, while Lisa takes Meg under her wing, determined to find something at which she excels.
Meanwhile Marge and Lois ditch housework for a bonding session and Peter and Homer fight over whose town has the better beer: Quahog's Pawtucket or Springfield's Duff.
In its announcement, Fox offered reaction from the animated patriarchs.
"Fox hasn't spent this much money since they took Simon Cowell tight T-shirt shopping," Peter Griffin said.
Homer Simpson added: "Finally I can get my hands on this guy!"
The shows have poked fun at each other over the years - one episode of the Simpsons features Italian police looking through a book of criminals, in which Peter Griffin's picture appears.
Another episode of Family Guy features a dozen Simpson characters sitting on the jury where Peter is standing trial for drug possession.
However the rivalry has grown more friendly recently, with Family Guy creator Seth MacFarlane voicing a prominent character in the The Simpson's 24th series finale.