The pilot will star Michael Sheen and Lizzy Caplan as William Masters and Virginia Johnson, two researchers who sparked a sexual revolution.
Gossip Girl actress Fitzgerald will play Libby Masters, the wife of Sheen's character, according to Deadline.
She recently starred in the movie Newlyweds and has also appeared in episodes of Blue Bloods and Law & Order: SVU.
An adaptation of the book by Thomas Maier, the Masters of Sex pilot will be directed by The Best Exotic Marigold Hotel's John Madden.
Paul Bettany was originally attached to the project, but later dropped out and was replaced by Sheen.
Showtime is developing a number of other pilots, including drama Ray Donovan starring Liev Schreiber and House actor Peter Jacobson.
> Teddy Sears, Nicholas D'Agosto join Showtime pilot Masters & Johnson