Francine Lifton was born to an Orthodox Jewish-American family and raised in New York City. She attended the all-girls Shulamith School in Borough Park, Brooklyn. She graduated magna cum laude from Brooklyn College, where she was elected to Phi Beta Kappa. She then earned a bachelor's degree in Hebrew literature from the Jewish Theological Seminary, and a master's degree in art history from the Institute of Fine Arts.
She married Dr. Samuel Klagsbrun, with whom she has a daughter. Francine Klagsbrun became executive editor at Encyclopedia Americana and World Book Encyclopedia. Her earliest books were written for children; more recent publications have reflected her interest in feminism and Judaism. She has written about 25 books and numerous written articles for Ms. Magazine and others. She edited both The First Ms. Reader (1973) and Free to Be ... You and Me (1974). She is widely known as a passionate advocate for ordaining women as rabbis, writing and lecturing extensively on the subject. She is also a leader in causes concerning women in Jewish religious life. Her relationship with her older brother motivated her to write Mixed Feelings (1992), on the sibling bond. She has served as chairwoman of the Board of Overseers of the Jewish Theological Seminary Library, secretary of the Board of Trustees of the Jewish Museum, and co-chair of its Exhibitions Committee. She has been a member of the Publication Committee of the Jewish Publication Society of America and the Board of Directors of the National Jewish Book Council. She is also on the Board of Directors of Lilith Magazine and the Editorial Board of Hadassah Magazine.
She writes a popular monthly column for the Jewish Week called "Thinking Aloud" and is working on a biography of Golda Meir.