McClanahan was born in Healdton, Oklahoma, on February 21, 1934. She was the daughter of Dreda Rheua-Nell (née Medaris, which is a Portuguese or Galician surname variation of Madeiros), a beautician, and William Edwin "Bill" McClanahan (July 4, 1908 – February 20, 1999) a building contractor.
She was raised Methodist and was of Irish and Choctaw ancestry. Her Choctaw great-grandfather was named Running Hawk according to her autobiography My First Five Husbands... and the Ones Who Got Away (2007). She grew up in Ardmore, Oklahoma; she graduated from Ardmore High School, where she acted in school plays and won the gold medal in oration. A National Honor Society member, she earned a bachelor of arts degree, cum laude, at the University of Tulsa, where she majored in German and theater, and joined the Kappa Alpha Theta sorority, serving as vice-president.
A life member of the Actors Studio, McClanahan made her professional stage début at Pennsylvania's Erie Playhouse in 1957, in the play Inherit the Wind. She began acting off-Broadway in New York City in 1957, but did not make her Broadway début until 1969, when she portrayed Sally Weber in the original production of John Sebastian and Murray Schisgal's musical, Jimmy Shine, with Dustin Hoffman in the title role.
Her role as Caroline Johnson on Another World (from July 1970 to September 1971) brought her notice. On the show, while taking care of twins Michael and Marianne Randolph, Caroline fell in love with their father, John, and began poisoning their mother, Pat. The short-term role was extended to more than a year before Caroline was finally brought to justice after kidnapping the twins. Once her role on Another World ended, McClanahan joined the cast of the CBS soap opera Where the Heart Is, in which she played Margaret Jardin.
On Maude, broadcast from 1972 to 1978, McClanahan played Maude's (Bea Arthur) best friend, Vivian Harmon, wife of Dr. Arthur Harmon (Conrad Bain).
On Mama's Family (1983–90), McClanahan portrayed uptight spinster sister Fran Crowley to Mama Harper (Vicki Lawrence), who was also a journalist for the local paper. McClanahan appeared on the series for two seasons before the show was revamped.
On The Golden Girls (1985–1992) and its short-lived successor The Golden Palace, McClanahan portrayed man-crazed Southern belle Blanche Devereaux, owner of the house she lived in and rented out to her three roommates and best friends: Dorothy Zbornak (Beatrice Arthur), Rose Nylund (Betty White), and Sophia Petrillo (Estelle Getty). McClanahan received an Emmy Award in 1987 for Outstanding Lead Actress in a Comedy Series for her work on the show.
She also appeared as a leader of Al-Anon in a 1970s informational film called Slight Drinking Problem, in which Patty Duke played the enabling and eventually self-empowered wife of an alcoholic. In feature films, she appeared in The Rotten Apple (1961) and Walk the Angry Beach (1968). She played a vicious fag hag in the film Some of My Best Friends Are... (1971), which was set in a gay bar. She appeared in the Walter Matthau-Jack Lemmon comedy Out to Sea (1998).
On television, she appeared as Matilda Joslyn Gage, mother-in-law of L. Frank Baum in the made-for-TV movie The Dreamer of Oz (1990). She made guest appearances on Murder, She Wrote and Newhart. In the early 1990s, McClanahan appeared as Margaret Becker in a trilogy of made-for-television films, Children of the Bride, Baby of the Bride, and Mother of the Bride. She voice-acted in cartoons, voicing Scarlett in the 1997 Fox Christmas special Annabelle's Wish. She played the role of Steve's grandmother in the Blue's Clues video Blue's Big Treasure Hunt (1999). On Spider-Man: The Animated Series, she appeared in the 1994 episode "Doctor Octopus: Armed And Dangerous" as Anastasia Hardy. She voiced the role of Bunny in a 2007 episode of King of the Hill, "Hair Today, Gone Today". In 2009, she appeared in an episode of Law & Order as a woman who had an affair with John F. Kennedy.
On Broadway, McClanahan replaced Tammy Grimes as "The Visitor from New York" (Hannah Warren) in the Neil Simon comedy California Suite from April 4, 1977 until the show closed on July 2 of that same year.
An animal welfare advocate and vegetarian, McClanahan was one of the first celebrity supporters of People for the Ethical Treatment of Animals. She supported Alley Cat Allies, a nonprofit advocacy organization dedicated to transforming communities to protect and improve the lives of cats, and appeared in a public service announcement for the organization in early 2010.
A liberal Democrat, in December 2003, she wrote a letter informing Democratic presidential nominee John Kerry that his pheasant hunting had cost him her vote and respect. In a July 2008 interview, she weighed in on the 2008 Presidential campaigns. Regarding Barack Obama, she said:
This is the damnedest election I've ever lived through, and Obama is the most amazing candidate I've ever bumped into. The man has unshakable integrity. He's the nearest thing to Lincoln we've seen.
In 2003, she appeared alongside Mark Hamill in the two-hander Six Dance Lessons in Six Weeks at the Coconut Grove Playhouse in Miami. She chose not to continue with the production and was replaced by Polly Bergen for the Broadway performances. The same year, she appeared in the musical romantic comedy film The Fighting Temptations as Nancy Stringer, which costarred Cuba Gooding, Jr., Beyoncé Knowles, Mike Epps, and Steve Harvey. On Broadway, she replaced Carole Shelley as Madame Morrible in the musical Wicked on May 31, 2005. She played the role for eight months until January 8, 2006. She was replaced by Carol Kane on January 10, 2006.
Her autobiography, My First Five Husbands ... and the Ones Who Got Away, was released in 2007.
In June 2008, The Golden Girls was awarded the 'Pop Culture' award at the Sixth Annual TV Land Awards. McClanahan accepted the award with costars Bea Arthur and Betty White.
McClanahan's final acting role was in the cable series Sordid Lives on the Logo network, which premiered July 23, 2008, playing Peggy Ingram.
McClanahan was a supporter of gay rights, including advocating for same-sex marriage in the United States. In January 2009, she appeared in the star-studded "Defying Inequality: The Broadway Concert – A Celebrity Benefit for Equal Rights".
In June 1997, McClanahan was diagnosed with breast cancer, for which she was treated successfully.
On November 14, 2009, she was to be honored for her lifetime achievements at an event "Golden: A Gala Tribute to Rue McClanahan" at the Castro Theatre in San Francisco, California. The event was postponed due to McClanahan's hospitalization. She had triple bypass surgery on November 4. It was announced on January 14, 2010, by Entertainment Tonight that, while recovering from surgery, she had suffered a minor stroke. In March 2010, fellow Golden Girls cast member Betty White reported on The Ellen DeGeneres Show that McClanahan was doing well and that her speech had returned to normal.
McClanahan died on June 3, 2010, at age 76, at New York–Presbyterian Hospital after she suffered a brain hemorrhage. After cremation, her ashes were given to her family.
Betty White told Entertainment Tonight that McClanahan was a "close and dear friend".
McClanahan was survived by her sixth husband, Morrow Wilson (from whom she separated in 2009); her son from her first marriage, Mark Bish of Austin, Texas; her sister, Melinda L. McClanahan, of Silver City, New Mexico; nephews, Brendan and Sean Kinkade, and nieces Marcia and Amelia. No funeral service was held for McClanahan, so her family created an official memorial page on Facebook, and memorial services were held during the summer of 2010 in New York and Los Angeles. On June 10, 2010, her New York apartment went on the market for an asking price of $3.95 million.
In 2017, a Golden Girls-themed eatery named Rue La Rue Cafe, owned by McClanahan's close friend Michael La Rue (who inherited many of the star's personal belongings and in turn decorated the restaurant with them), opened in the Washington Heights section of the New York City borough of Manhattan.The Rotten Apple (1961)
Angel's Flight (1965)
Walk the Angry Beach (1968)
Hollywood After Dark (1968)
The Unholy Choice (1968)
The People Next Door (1970)
Some of My Best Friends Are... (1971)
The Pursuit of Happiness (1971)
They Might Be Giants (1971)
Rainbow: The Stormy Life of Judy Garland (1978 TV Movie)
The Skin of Our Teeth (1983)
Little Match Girl (1987)
Take My Daughters Please (1988)
Children of the Bride (1990)
After the Shock (1990)
The Earth Day Special (1990)
Message from Nam (1993)
Mother of the Bride (1993)
A Holiday to Remember (1995)
Dear God (1996)
Innocent Victims (TV movie) (1996)
Annabelle's Wish (1997)
Out to Sea (1997)
Starship Troopers (1997)
Rusty: The Great Rescue (1998)
A Burning Passion (1999)
The Fighting Temptations (2003)
Back to You and Me (2005)
Baby of the Bride (2006)
Miracle Dogs (2007)
Generation Gap (2008)