A native of Athens, Georgia, and principal of a women's college, Safford applied to the (Southern) Presbyterian Church, U.S. (PCUS) for missionary service in 1873. She was appointed for women's work in Soochow (Suzhou) and sailed shortly thereafter. As a seasoned educator, she developed a systematic, holistic approach to the cause of women that included village itineration, home visitation, and special classes and worship services just for women. Because of poor health, she was often in pain; during such times when she was unable to itinerate, she turned to the preparation of literature, her most lasting achievement. She wrote or translated a dozen or more books and pamphlets in a style that simple women could understand. As editor of the interdenominational magazine Woman's Work in the Far East, she was invited to address the historic 1890 missionary conference in Shanghai, but illness prevented her attending, and her paper was read to the assembly by a colleague. She died soon afterward and was buried in Shanghai.