- At age 43, she adopted her second child, a baby girl from Africa, named Ash. This is apparently a shortened version of her birth name, Aberash. The girl's full name is Caroline Aberash Parker.
- Split with actor Billy Crudup in November of 2003, after seven years. She was seven months pregnant with his child at the time.
- The Counting Crows song "Butterfly in Reverse" was written for her.
- [April 8, 2008] Broke up with her Weeds - Kleine Deals unter Nachbarn (2005) co-star, Jeffrey Dean Morgan. Later reconciled and became engaged and then broke engagement.
- Turned down the opportunity to replace Shannen Doherty on Charmed: Zauberhafte Hexen (1998).
- Has had a long-time close friendship with Counting Crows front man, Adam Duritz. Their birthdays are a day apart; he was born on August 1, 1964, she on August 2, 1964.
- Was author Stephenie Meyer's original choice for the role of "Esme Cullen" in the film adaptation of her novel, Twilight - Biss zum Morgengrauen (2008).
- Graduated from the prestigious North Carolina School of Arts.
- Son, William Atticus, born 7 January 2004.
- Won Broadway's 2001 Tony Award as Best Actress (Play) for "Proof." She had previously received a Tony nomination in the same category in 1990 for "Prelude to a Kiss."
- Considered for the role of Susan Mayer in Desperate Housewives (2004).
- Nominated for the 2005 Tony Award for "Reckless" (Best Performance by a Leading Actress in a Play).
- Her favorite movie growing up was Heimweh nach St. Louis (1944).
- Loves Corona beer. Loves to listen to albums by Willie Nelson, Frank Sinatra, Chet Baker and Tom Waits.
- Mary-Louise's maternal grandfather was the son of Swedish immigrants. Her other ancestry includes English, Scottish, Scottish-Irish, German, and Dutch.
- Performed in "Proof," which first opened at Manhattan Theatre Club, then moving to Broadway. She won the Tony award for Best Actress in a Play for this in 2001.
- Her critically acclaimed role as a jaded London prostitute named Poopay in "Communicating Doors" played in New York City at the Variety Arts Theatre on Third Avenue, 1998.
- Has supported LGBT youth, AIDS foundation, Worldwide Orphans foundation, Hope North for Ugandan child soldiers and victims.
- Graduated high school from North Carolina School of the Arts with a concentration in acting along with Dane DeHaan, Hannah Telle, and Anthony Mackie.
- Graduate of Marcos de Niza High School in Tempe, AZ., class of 1982.
- Received the Ally Award, which honors her as an LGBT rights advocate, in 2016.
- Listed as one of twelve "Promising New Actors of 1990" in John Willis' Screen World, Vol. 42.
- For the film The Best Thief in the World (2004), originally Eric Stoltz was offered the role of her husband, but Mary-Louise Parker wanted someone older so asked the producers to hire the actor David Warshofsky. The film never received a theatrical release.
- Good friend of Shelby Lynne.
- Hated school.
- Her father, John Morgan Parker, a judge who served in the U.S. Army. Because of her father's career, Parker spent parts of her childhood in South Carolina, Tennessee, and Texas, as well as in Thailand, Germany, and France.
- Double Tony best actress winner for both Proof and The Sound Inside.
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