Richard Cohen, a columnist for The Washington Post and friend of Ephron, was among those who reported her passing in a New York hospital on Tuesday evening (June 26).
Ephron's son Jacob Bernstein told the New York Times that his mother died of pneumonia brought on by acute myeloid leukemia. Ephron - who had the blood condition myelodysplasia, which can cause leukaemia - was reported to have been seriously ill earlier on Tuesday.
Nominated for an Oscar on three occasions, Ephron's best-known screenplays included When Harry Met Sally, Sleepless in Seattle and You've Got Mail. Her most recent movie was 2009's Julie & Julia, starring frequent collaborator Meryl Streep.
[L-R: Nora Ephron with 'Julie & Julia' stars Meryl Streep and Amy Adams in 2009; with Tom Hanks in 2002]
A director, writer and producer, Ephron was born in New York City on May 19, 1941, moving to Beverly Hills at the age of 4.
Ephron worked as an intern for former US president John F Kennedy during the early 1960s, and became a journalist for the New York Post soon after. One of her earliest scoops was the news of Bob Dylan's secret marriage to his first wife Sara Lownds.
She also became known for her satirical pieces - writing for publications including Esquire, Cosmopolitan and the New York Times Magazine - stage plays and books, including several collections of reflective essays.
Ephron was married firstly to Dan Greenburg and secondly to investigative journalist Carl Bernstein, who broke the Watergate scandal with Bob Woodward during the 1970s.
She is survived by her third husband Nicholas Pileggi, Jacob and Max, her two sons with Bernstein, and her sisters Delia and Amy.