She died of leukemia Tuesday night at New York Presbyterian/Weill Cornell Medical Center, her family said in a statement.
"She was so, so alive," said her friend Carrie Fisher. "It makes no sense to me that she isn't alive anymore."
Born into a family of screenwriters, Ephron was a top journalist in her 20s and 30s, then a best-selling author and successful director. Loved, respected and feared for her devastating and diverting wit, she was among the most quotable and influential writers of her generation.
She wrote and directed such favorites as "Julie & Julia" and "Sleepless in Seattle," and her books included the novel "Heartburn," a roman a clef about her marriage to Washington Post reporter Carl Bernstein; and the popular essay collections "I Feel Bad About My Neck" and "I Remember Nothing."
She was tough on others — Bernstein's marital transgressions were immortalized in "Heartburn" — and relentless about herself. She wrote openly about her difficult childhood, her failed relationships, her doubts about her physical appearance and the hated intrusion of age.
Even within the smart-talking axis of New York-Washington-Los Angeles, no one bettered Ephron, slender and dark-haired, her bright and pointed smile like a one-liner made flesh. Friends from Mike Nichols and Meryl Streep to Calvin Trillin and Pete Hamill adored her for her wisdom, her loyalty and turns of phrase.
As a screenwriter, Ephron was nominated three times for Academy Awards, for "Silkwood," ''When Harry Met Sally ..." and "Sleepless in Seattle," and was the rare woman to write, direct and produce Hollywood movies. Fisher and Meg Ryan were among the many actresses who said they loved working with Ephron because she understood them so much better than did her male peers.
"I suppose you could say Nora was my ideal," Fisher said. "In a world where we're told that you can't have it all, Nora consistently proved that adage wrong. A writer, director, wife, mother, chef, wit — there didn't seem to be anything she couldn't do."
"Sleepless in Seattle" star Tom Hanks said Ephron "knew what was important to know; how things really worked, what was worthwhile, who was fascinating and why."
The eldest of four children, Ephron was born in New York to screenwriters Harry and Phoebe Ephron, who moved to Beverly Hills, Calif., when she was 4 years old.
Regular visitors included "Casablanca" co-writer Julius J. Epstein, "Sunset Boulevard" collaborator Charles Brackett, and the team of Albert Hackett and Frances Goodrich, who worked on "The Thin Man" and "It's a Wonderful Life."
Determined by high school to be a journalist, Ephron graduated from the single-sex Wellesley College in 1962, moved to New York and started out as a "mail girl" and fact checker at Newsweek. A newspaper strike at the end of the year gave her a chance. Victor Navasky, the future editor of The Nation, was then running a satirical magazine called the Monacle. He was working on a parody of the New York Post, "The New York Pest," and asked Ephron for a spoof of Post columnist Leonard Lyons.
She succeeded so well that the newspaper's publisher, Dorothy Schiff, reasoned that anyone who could make fun of the Post could also write for it. Ephron was asked to try out as a reporter. Within a week, she had a permanent job and remained there five years.
Ephron began writing for Esquire and The New York Times and developed a national following as a throwback to the prime of Dorothy Parker and S.J. Perelman and a worthy peer of such new and hip journalists as Gay Talese and Tom Wolfe. Part of her gift was her fresh takes on such traditional subjects for women as food and fashion.
By the 1970s, she had met Bernstein, who teamed with fellow Washington Post reporter Bob Woodward on prize-winning coverage of the Watergate scandal that brought down President Richard Nixon. They married in 1976, and had two children, but love soon turned to hate — and matured into art. Ephron was pregnant with their second child when she learned Bernstein was having an affair.
She wrote "Heartburn," later a film starring Streep and Jack Nicholson and directed by Nichols, with whom she collaborated often. The book was so close to her life that Bernstein threatened to sue.
Another perk from her time with Bernstein: She sussed out that "Deep Throat," the unnamed and unknown Watergate source, was in fact FBI official Mark Felt. She would allege that she told countless people about Felt, who did not acknowledge his role until years later.
Her screenwriting credits included "Heartburn," the nuclear power drama "Silkwood" and the romantic comedy "When Harry Met Sally ..." She twice directed the team of Ryan and Hanks, in "Sleepless in Seattle" and "You've Got Mail," and also worked with John Travolta (in the fantasy "Michael"), Steve Martin ("Mixed Nuts") and Nicole Kidman ("Bewitched").
Ephron was married three times: to Dan Greenburg, Bernstein and to "Wiseguys" author Nicholas Pileggi, whose book was adapted into the Martin Scorsese film "Goodfellas." Sisters Delia, Amy and Hallie Ephron also are writers and Nora and Delia collaborated on such films as "This Is My Life" and "Sleepless in Seattle."