DiFalco began her news career at ABC in New York in 1986 as an unpaid intern in postproduction for 20/20, a news magazine show. She was later assigned to "Close Up" as a production secretary. She eventually worked for Peter Jennings's documentary unit, producing shows on abortion and gun control, and covering foreign policy stories in Cambodia, Haiti and India.

In 1991, DiFalco was stationed in Israel and reported on the SCUD missile attacks during the Gulf War. In 2003, during the War on Afghanistan, she spent six weeks in Khandahar, embedded with an infantry unit of the 101st Airborne Division. She produced segments for an ABC-TV show called Profiles From the Frontline. She has won several awards, including three Emmy, one for a story she produced on land mines in Cambodia, and a Peabody.

On August 27, 1994, DiFalco married fellow ABC News producer Anthony Radziwill in East Hampton, New York. Radziwill was the only son of prince Stanislas Radziwill and Lee Radziwill. He died on August 10, 1999 at age 40 after a five-year battle with cancer.

After her husband's death, Radziwill left ABC News to write a memoir about her childhood, her career at ABC News, as well as her effort to manage her husband's cancer. "What Remains: A Memoir of Fate, Friendship and Love" (Scribner, 2005) made the New York Times Best Seller list. A review of the book in the Times called it a "bittersweet account" that emphasized "graciousness over disclosure".

In 2006, Radziwill signed with Glamour magazine to write a monthly column called "Lunch Date". Her Lunch Dates have included former mayor Rudy Giuliani, and Hollywood actors Antonio Banderas, Rachel Weisz, and Alec Baldwin.