Ephron succumbed to pneumonia after battling acute myeloid leukemia.
"It is with great sadness that we report that Nora Ephron has died at the age of 71, after a battle with leukemia," Alfred A. Knopf of Knopf publishing said in a statement. "She brought an awful lot of people a tremendous amount of joy. She will be sorely missed."
Ephron, also known for her satirical and humorous columns, got her start at the New York Post, and went on to write for Esquire and The New York Times Magazine. Following her graduation from Wellesley College in 1962, she even had a brief stint as an intern in the Kennedy White House.
Ephron came from a family of screenwriters — her mother, father and two of her sisters all shared the profession. Ephron's first big hit was When Harry Met Sally... in 1989. Starring Billy Crystal and Meg Ryan, the romantic comedy about friends becoming lovers, was an instant hit, raking in $92.8 million at the box office. It includes one of cinemas' most hilarious lines after Ryan fakes an orgasm in a deli: "I'll have what she's having," which was said by a patron portrayed by director Rob Reiner's mother.
Ephron reunited with Ryan in Sleepless in Seattle, which she co-wrote with her sister Delia. Ryan and Tom Hanks starred in the film, which landed them, and the film, Golden Globe nominations. The pair would reunite five years later in Ephron's You've Got Mail. Both films were very successful, bringing in $227.8 million and $250.8 million, respectively.
Her most recent film, Julie and Julia, which she wrote and directed, was a critical darling. It scored many major award nominations. Meryl Streep won Best Actress at the Golden Globes for her portrayal of Julia Child. Streep had also starred alongside Jack Nicholson in one of Ephron's early works, 1986's Heartburn, which was based on her then-husband Carl Bernstein's affair.
Ephron personally received three Oscar nominations for Best Screenplay — for Silkwood, When Harry Met Sally... and Sleepless in Seattle.
Among her other projects include two collections of essays — I Feel Bad About My Neck: And Other Thoughts on Being a Woman and I Remember Nothing — two plays called Imaginary Friends and Love, Loss and What I Wore, and a blog for The Huffington Post.
Ephron is survived by her third husband Nicholas Pileggi and her sons Jacob and Max Bernstein.