Her husband, Tony Award-winning playwright David Rabe, said she died after a 21-year battle with chronic lymphocytic leukemia. She was surrounded by her family and brother when she died at her home in Lakeville, Conn., he said.
She dealt with the disease courageously, quietly and privately, Rabe said, and conducted herself with enormous grace "and made it into an opportunity for her children to grow and be human."
Clayburgh came from a privileged New York family. Her father was vice president of two large companies, and her mother was a secretary for Broadway producer David Merrick. Her grandmother, Alma Clayburgh, was an opera singer and New York socialite.
Growing up in a such a rich cultural mix, she could easily have been overwhelmed. Instead, as she said in interviews, she asserted herself with willful and destructive behavior - so much so that her parents took her to a psychiatrist when she was 9.
She escaped into a fantasy world of her own devising. She was entranced by seeing Jean Arthur play "Peter Pan" on Broadway, and she and a school chum concocted their own dramatics every day at home. She became serious-minded at Sarah Lawrence College, concentrating on religion, philosophy and literature.
Clayburgh also took drama classes at Sarah Lawrence. She and her friend Robert De Niro acted in a film, "The Wedding Party," directed by a Sarah Lawrence graduate, Brian DePalma. After graduating with a bachelor of arts degree, she began performing in repertory and in Broadway musicals such as "The Rothschilds" and "Pippin."
Alongside Richard Thomas, she headed the 2005 Broadway cast of "A Naked Girl on the Appian Way," Richard Greenberg's comedy about one family's unusual domestic tribulations.
Director Doug Hughes, who directed her in a production of Arthur Miller's "All My Sons" at the Westport Country Playhouse two years ago, called her for "Naked Girl."
"That she has the time to do a run of a play is just an extraordinary boon because I've had the pleasure of seeing her play a bona fide tragic American role beautifully, and I have had the pleasure of directing her in a very, very smart light comedy and be utterly brilliant in that," he said in 2005.
During an interview that year, Clayburgh explained the unglamorous side of acting.
"One of the funny things about actors is that people look at their careers in retrospect, as if they have a plan," she said.
"Mostly, you just get a call. You're just sitting there going, 'Oh, my God. I'm never going to work again. Oh, God. I'm too old. Maybe I should go and work for Howard Dean.' And then it changes."
Besides appearing in such movies as "I'm Dancing As Fast As I Can," "Silver Streak" and "Running With Scissors," Clayburgh's Broadway credits include Noel Coward's "Design for Living," the original production of Tom Stoppard's "Jumpers," and the Tony Award-winning musicals "Pippin" and "The Rothschilds."
Clayburgh was also nominated for an Academy Award for "Starting Over," a comedy about a divorced man, played by Burt Reynolds, who falls in love but can't get over his ex-wife. She appeared on TV shows including "Dirty Sexy Money" and was nominated for two Emmys: for best actress in 1975 for her work on "Hustling" and for her guest turn on "Nip/Tuck" on FX in 2005.
She is survived by three children, including actress Lily Rabe, Michael Rabe and stepson Jason Rabe.
There will be no funeral, Rabe said. The family will have a memorial in about six months, though plans have not been finalized.
Associated Press writer Rodrique Ngowi contributed to this report from Boston.