Secrest was born in Bath, England and educated there. Her family emigrated to Canada, where she began her career as a journalist. She worked as women's editor for the Hamilton News in Ontario, Canada; shortly thereafter she was named "Most Promising Young Writer" by the Canadian Women's Press Club. In 1964 she began writing for the Washington Post, doing profile interviews of notable personalities from Leonard Bernstein to Anaïs Nin.

In 1975 she left the Post to write books full-time. Since then she has written a number of critically-acclaimed biographies; her subjects have included Frank Lloyd Wright, Joseph Lord Duveen, Stephen Sondheim, Leonard Bernstein, Salvador Dali, Kenneth Clark, Bernard Berenson, Romaine Brooks, and Richard Rodgers. She has also published an autobiography entitled Shoot the Widow.

She now lives in Washington, D.C. .

Secrest's Being Bernard Berenson was a finalist for the Pulitzer Prize in 1980 and for the American Book Awards in 1981. In 2006 she received the National Humanities Medal.