Johnson grew up in Brooklyn, New York, the oldest of seven children in an "Irish Catholic family." As a young adult she joined the religious order of the Sisters of Saint Joseph whose motherhouse is in Brentwood, Long island, NY. She received a B.S. from Brentwood College in 1964, an M.A. from Manhattan College in 1964.
1981, she became the first woman to earn a Ph.D. in theology at the Catholic University of America (CUA). CUA is a pontifical university of the Catholic Church and is the only university in the U.S. founded and sponsored by America's bishops. Johnson recalls that her experience there was "rich, respectful, and collegial," but was also "lacking in female presence." During her studies there in the 1970s Johnson observes, "I never had a woman professor, I never read one woman author. There were none to be had. It was a totally male education." CUA attempted to remedy this when Johnson herself was hired into a tenure-track position in Christology. She became one of the first female theologians allowed to receive a doctorate by the church authorities, as a result of the "liberalization decrees that capped the Second Vatican Council." Feminism had begun impacting the thinking and dialog of female Catholic theologians, and pioneering feminist theologians Elisabeth Schüssler Fiorenza and Sandra M. Schneiders influenced Johnson on feminist topics, including using feminine metaphors and language for God. Inspired by their example, Johnson and other women graduate students formed a group, "Women in Theology."
She has served as head of the Catholic Theological Society of America and the American Theological Society.
While at CUA in 1980 she felt profoundly affected by events of the Salvadoran Civil War when four American women, including three nuns, working as missionaries and helping oppressed people to escape violence, were abducted and killed by a death squad. Johnson mourned the women, but she "redirected her anguish by carrying out their mission in her own field of theology."
Johnson notes that leaders of her religious community encouraged her to enter the field of theology and pushed her to continue in spite of obstacles. "When I applied for tenure at Catholic University, I received the full positive vote of the faculty. But the outcome was in doubt because some bishops were not happy with an article I had written," she says, referring to her article questioning the traditional view of Mary as "humble and obedient." Though she contemplated leaving rather than facing the "arduous process of interrogation," General Superior Sister John Raymond McGann advised her not to give up, and Johnson did receive tenure.
Johnson had taught science and religion at the elementary and high school level, then taught theology at St. Joseph's College (New York) and at CUA before moving to Fordham in 1991. At Fordham, she was named Distinguished Professor in 1997 and "Teacher of the Year" in 1998.