The actor was previously reported to be in negotiations to star in the forthcoming television adaptation of Thomas Maier's book Masters of Sex: The Life and Times of William Masters and Virginia Johnson, the Couple Who Taught America How to Love.
Bettany was supposed to play Masters, but he has since exited the project, according to Deadline.
Showtime is now looking for a replacement for Bettany, as well as an actress for the female lead. Lizzie Caplan is currently being discussed for the role of Johnson.
Bettany recently described The Avengers as the best job he has ever had. The actor voices Tony Stark's (Robert Downey Jr) Artificial Intelligence computer programme JARVIS in the film.
Bettany's wife Jennifer Connelly gave birth to a baby girl in May.
Watch the trailer for The Avengers below: