Called Mockingbird Lane, the show will be a darker take on the classic 1960s horror comedy.
Deadline reports that the Arrested Development star will play Lily Munster, the matriarch of the Munster clan.
She joins Jerry O'Connell and Eddie Izzard, who have been cast as Herman Munster and 'Grandpa', respectively.
True Blood actress Mariana Klaveno was originally cast as Lily Munster, until complications with her involvement in Desperate Housewives creator Marc Cherry's new pilot Devious Maids forced her to pull out of the project.
Mockingbird Lane has been written by Pushing Daisies creator Bryan Fuller, and is to be directed by X-Men helmer Bryan Singer.
This marks de Rossi's return to primetime television after the cancellation of her comedy Better Off Ted.