The "Story of My Life" singers will gather around a fire for a camping scene with troublesome cartoon baby Stewie, voiced by series creator Seth MACFarlane.
But not all the boys have lines in the scene - only Liam Payne and Louis Tomlinson recorded their voice for the episode, according to reports.
"There are not a lot of shows that, in the same season, feature guest-star appearances by both Frank Sinatra, Jr and One Direction," executive producers Richard Appel and Steve Callaghan said in a statement.
One Direction's "Family Guy" debut, in which Stewie scares
the lads with a tale about non-skinny jeans, will air in May (16).