A noted American journalist, essayist, writer as well as producer and director, Ephron wrote and directed her last film "Julia and Julia" in 2009, in which she worked once more alongside her good friend Meryl Streep.
"It is with great sadness that we report that Nora Ephron has died," her publisher Alfred A. Knopf said in a statement.
"She brought an awful lot of people a tremendous amount of joy. She will be sorely missed."
The New York Times cited her son, Jacob Bernstein, as saying Ephron died of pneumonia brought about by acute myeloid leukemia. Bernstein is a freelance reporter for the newspaper.
New York City Mayor Michael Bloomberg issued a statement calling the loss "a devastating one" for the city's arts and
"From her earliest days at New York City's newspapers to her biggest Hollywood successes, Nora always loved a good New York story, and she could tell them like no one else," Bloomberg said in a statement.
Ephron, who often parlayed her own love life into movies like "Heartburn" and gave her acerbic take on aging in the 2010 essay collection, "I Remember Nothing: And Other Reflections," had kept her illness largely private except for close friends and family.
"At some point, your luck is going to run out ... You are very aware with friends getting sick that it can end in a second," Ephron told Reuters news agency in a 2010 interview while promoting the book.
The elegant Ephron, known for habitually dressing in black, urged aging friends and readers to make the most of their lives.
"You should eat delicious things while you can still eat them, go to wonderful places while you still can ... and not have evenings where you say to yourself, 'What am I doing here? Why am I here? I am bored witless!'" she said. She began her career as a journalist but transitioned into movies, leaving behind a legacy of more than a dozen films, often featuring strong female characters, that she either wrote, produced or directed.