St. Mary's Orphanage, an institution of the Catholic Diocese of Galveston (now the Catholic Diocese of Galveston-Houston), was operated by the Sisters of Charity of the Incarnate Word from 1867 until 1968, when its functions were absorbed by the Family Life Services office of the diocese. The orphanage began in a building on the grounds of St. Mary's Infirmary and remained closely associated with the hospital for many years. The hospital had originally cared for orphans, but an increase in the number of both orphans and patients as a result of yellow fever epidemics necessitated a separate orphanage. On January 3, 1874, Bishop Claude Marie Dubuis of Galveston purchased the Green Bayou Place and a thirty-five-acre tract of land on the beach about three miles west of Galveston. In February 1874 twenty-eight orphans were moved to the new St. Mary's Orphan Asylum. An additional two-story frame building was soon erected and was formally dedicated by Bishop Dubuis on the feast of the Maternity of Our Lady, October 11, 1874. This building was used for girls, and the Green Bayou residence was given to boys. The rule was to keep girls until they were eighteen years old, while boys were usually kept until the age of ten, when they were sent to St. Mary's College to continue their education.
Early in its history the orphanage fell prey to a series of disasters. In 1875 one of the old buildings that housed twelve children under two years old was destroyed by fire; no lives were lost. Between September 15 and 17 of that year a severe storm completely destroyed the old Green Bayou residence and badly damaged the new building. In the months following the storm, concerts and entertainments were held in Galveston for the benefit of storm victims. St. Mary's was one of the beneficiaries and used the money received to repair the girls' building. The boys' building was not replaced until four years later, when the orphanage received a $10,000 gift from St. Mary's Infirmary.
Financial support for the orphanage came from a variety of sources over the institution's hundred-year history. St. Mary's Infirmary and St. Mary's Orphanage were administered as a single institution until April 25, 1883. The sisters also depended on begging for alms as a significant source of income. Benefits, popular appeals, and public-school funds also contributed. In 1879 a group of Galveston businessmen formed the Galveston Orphans Association to help meet the orphanage's financial needs. Begging continued to provide additional income until Bishop Nicholas A. Gallagher forbade the practice in 1896. In November of that year St. Mary's Orphan's Asylum was chartered as a corporation dependent primarily on business contributions, and a decision was made to sell the existing orphanage and build a new one closer to the center of Galveston. The orphanage remained at Green's Bayou, however, until the buildings were washed away by the onslaught of the Galveston hurricane of 1900. All ten sisters drowned, and only three of the orphanage's ninety-four children survived. Shortly after the storm Bishop Gallagher purchased a new orphanage site on 40th and Q streets, known as the Wharton Davenport Estates, and the orphans, who had been staying at the infirmary, were moved to a large frame house there in 1901. A year later ninety orphans and a staff of nine sisters occupied a new brick building on the site.
In 1925 St. Mary's Orphanage began receiving Community Chest aid and in 1942 was placed under the general supervision of Catholic Charities. On June 20, 1950, Most Rev. Wendelin J. Nold, bishop of Galveston, blessed a new three-story building, which replaced the 1901 structure. The sisters continued to provide elementary education for the children until the 1960s, when the orphans were enrolled in the city's parochial schools. During the 1960s the care of dependent children shifted from institutions to foster homes. Many of the children in orphanages were no longer orphans but victims of broken homes. By 1965 the average daily number of children cared for in St. Mary's Orphanage was only twenty-one. In 1967 Bishop Nold and the Orphan Association decided to close the orphanage. The buildings were sold and the proceeds put into a trust fund to care for children under the direction of Galveston Family Life Services.