Born in Birmingham, Alabama to a minister and his wife, both deaf, she was taught to speak by a hearing aunt, who also introduced her to acting.

After attending the University of North Carolina, she traveled to Los Angeles, California, where she found work as a secretary by day and took acting lessons by night.

She began appearing in several television productions, but married Jerry Bick and took time off to raise her 2 children; she eventually divorced Bick, who died in 2004.

In 1974, she returned to film in Thieves Like Us. Milos Forman saw her, and cast her (possibly because of her height and bearing) as McMurphy's nemesis Nurse Ratched in One Flew Over the Cuckoo's Nest, for which she won the Oscar for Best Actress. She also appeared in such films as The Cheap Detective, Exorcist II: The Heretic, Firestarter, Brainstorm, Flowers in the Attic and as Sebastian's aunt in Cruel Intentions.

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.

She stands at 5'9 1/2".