In 1974, she returned to film in Thieves Like Us. Milos Forman saw her, and cast her in One Flew Over the Cuckoo's Nest, for which she won the Academy Award for Best Actress. She also appeared in such films as The Cheap Detective, Exorcist II: The Heretic, Firestarter, Brainstorm and Flowers in the Attic.
Fletcher was nominated for an Emmy Award for her recurring role on the television series Picket Fences. She also had a continuing role in Star Trek: Deep Space Nine as the scheming double-faced Bajoran religious leader Kai Winn Adami.