A native of the New York City area, Duffy attended Wellesley College. As a young woman, she had letters published in Marvel Comics letter columns in the mid-1970s. Her first credits as editor appear on The Incredible Hulk #231 and The Spectacular Spider-Man #26, both cover dated January 1979. She edited the first seventeen issues of Marvel's ROM series, before handing over the reins to Al Milgrom.

Her writing work included Power Man and Iron Fist, Marvel's Star Wars comic, Conan the Barbarian, and Wolverine. Among other things, she created the team and most of the members of the Fallen Angels.

In the 1990s, she worked for other publishers, including DC Comics, where she wrote the first 14 issues of Catwoman (1993). For Rob Liefeld's Extreme Studios imprint of Image Comics, she wrote all twenty-two issues of the first Glory series, between March 1995 and April 1997, the last five issues of which were released by Liefeld's Maximum Press after his departure from Image.

In the early 2000s, she wrote issues of Marvel's Defenders, while working at a financial services company in Lower Manhattan, to which she would commute from New Jersey. Her work at that company includes meeting planning, as well as editing, proofreading, and packaging for a comic book published by the company.

As of October 2001, Duffy was recovering from a surgery following an accident that caused major trauma to the bones in the lower half of her right leg. As her company's offices are located eight blocks from the World Trade Center site, Duffy and her coworkers were evacuated on the day of the September 11 attacks.