Born in Birmingham, Alabama to Episcopal minister Robert Fletcher and his wife Estelle, both of whom were deaf, Louise Fletcher was introduced to performing at a young age by the aunt who taught her to speak. After graduating from the University of North Carolina - Chapel Hill, she took a trip out west with her roommates, finding herself in Los Angeles without enough money to return home. She took a temporary job as a receptionist and signed up for acting classes at night. Soon she was working regularly in television and film, but after marrying producer Jerry Bick and having two sons, the actress took a long hiatus to raise her children.

Returning to work in 1974 in Robert Altman's Thieves Like Us, Fletcher came to the attention of director Milos Forman, who was casting the difficult role of the nurse in One Flew Over the Cuckoo's Nest. She won the role - and then the Academy Award - portraying deadly, inflexible Nurse Ratched, who has since become a cultural icon. Numerous film roles followed, including co-starring turns with Peter Falk in The Cheap Detective and with Richard Burton in Exorcist II: The Heretic. Fletcher has appeared in a number of science fiction and horror classics such as Firestarter, Brainstorm, and Flowers in the Attic.

Though she earned an Emmy Award nomination for her recurring role on Picket Fences, Fletcher is perhaps best known to recent television audiences as Kai Winn from Star Trek: Deep Space Nine and as Nora Bloom from the cult classic VR.5.
Learned sign language at a very young age, as both of her parents were deaf. Lily Tomlin's role in Robert Altman's Nashville was originally written for, and in part by, Fletcher, whose then-husband had been Altman's producer. When the two men had a falling-out, Altman chose to cast Tomlin instead. Was a leading choice to play the mother in Terms of Endearment. After her divorce from producer Jerry Bick in the late 1970s she caused a stir when she, then in her 40s, began dating 21-year-old Morgan Mason, the son of actor James Mason. Her role in One Flew Over the Cuckoo's Nest had been turned down by Anne Bancroft, Ellen Burstyn, Colleen Dewhurst and Jane Fonda. Bancroft and Dewhurst turned down the role because they found it anti-feminist and downright misogynistic. Was cited for reckless driving in 2000 when she slammed into a police car near her Virginia home. Her Oscar-winning role as Nurse Ratched in One Flew Over the Cuckoo's Nest was ranked #5 in the American Film Institute's Villains list in their 100 years of The Greatest Screen Heroes and Villains. One of the other Best Actress nominees in 1976 was Ann-Margret, who was nominated for her role Tommy. Coincidentally, both films featured Jack Nicholson.