St. Francis Xavier Hospital was founded by the Sisters of Charity of Our Lady of Mercy. It opened in 1882 as Saint Francis Infirmary with fifteen beds, five staff nurses, and two surgeons.
In 1896, a two-story wooden addition containing two wards, 20 private rooms with baths, and an operating room was completed. By the close of the century, however, the average daily census had increased to 50 patients, and the need for more space became acute. In early 1900, another two-story building was erected adding 18 additional patient rooms, another operating room, a dining area and a chapel.
The Sisters also responded to the increasing need for trained nurses by establishing the St. Francis Xavier Infirmary Training School for Nurses which opened on October 22, 1900.
During World War I, no resources were available to improve facilities at the Infirmary. After the war ended, however, the Sisters raised $161,515 in funds and on July 5, 1925 broke ground to build a new three and a half story Spanish-style St. Francis Infirmary facing Calhoun Street. In addition to patient rooms, the new facility also housed laboratory and x-ray services and an emergency room.
As the Charleston population grew, so did the facility. In keeping with this growth, the name of the Infirmary was legally changed to St. Francis Xavier Hospital on December 31, 1951 and construction continued throughout the 1970s and 1980s ensuring that the Hospital remained responsive to the health care needs of the community.