Organized in 1866, this institution was the first private hospital established in the state. Originally known as Charity Hospital, it was founded by three French Catholic Sisters, members in the Order of Sisters of Charity of the Incarnate Word. Constructed on this site, which had been part of Fort Scurry during the Civil War, the hospital opened for patients on April 1, 1867.
The new hospital proved to be a vital addition to the health care facilities of the area. Three months after it was opened, a yellow fever epidemic struck the city. One victim of the disease was the hospital Superior, Mother M. Blandine. Following the epidemic an orphanage and school were established here by the Sisters for children whose parents died of the sickness. The school was closed and the orphanage was later moved to another site in Galveston.
St. Mary's played a significant role in the aftermath of two area disasters. In 1900, despite heavy damage caused by a hurricane, the hospital remained open for the treatment of storm victims. In 1947 health care was provided here for many of the thousands injured in a series of chemical explosions and fires at the port of Texas City (8 mi. NW).