Mary-Louise Parker was born on August 2, 1964, in Fort Jackson, South Carolina, to Judge John Morgan Parker and Caroline Louise Morell. She is of mostly Swedish, English, and Scottish descent.
Her father's occupation led the family to travel around the country and abroad, which had a significant impact on her upbringing. Parker showed an early interest in acting and majored in the subject during her college years, graduating from the North Carolina School of the Arts.
She began her acting career with a role on the daytime soap Ryan's Hope in 1975, before transitioning to the off-Broadway stage in the late 1980s. Parker made her Broadway debut in 1990 with the play "Prelude to a Kiss," earning several awards and nominations, including a Tony nomination.
Parker's breakthrough role came in 1991 with the film Fried Green Tomatoes, where she played a feisty and memorable character. She went on to appear in a range of films and TV shows, including Longtime Companion, Grand Canyon, Naked in New York, Bullets Over Broadway, The Client, Boys on the Side, The Portrait of a Lady, The Maker, Let the Devil Wear Black, Red Dragon, and Pipe Dream.
Parker is known for her versatility and willingness to take on offbeat roles in independent films and stage productions. She has won numerous awards for her work, including a Tony Award for her performance in the play "Proof" in 2000.
In addition to her film and stage work, Parker has also had a successful TV career, earning critical acclaim for her roles in the TV miniseries Angels in America and the TV series Weeds. She has also appeared in several films, including RED 2, R.I.P.D., Jamesy Boy, Behaving Badly, Chronically Metropolitan, Golden Exits, and Red Sparrow.
Parker has been in a long-term relationship with actor Billy Crudup, with whom she has a son, William Atticus Parker. She has also adopted a second child from Ethiopia and has been involved in several charitable organizations, including Hope North, which works to educate and heal young victims of Uganda's civil war.
In 2015, Parker published her memoir-in-letters, Dear Mr. You, which explores her experiences as a mother and her struggles with love and relationships.