St. Mary's was located at 126 Edward Street, at the corner of Morgan Street (now South Elmwood Avenue).

Prior to establishment and incorporation on January 13, 1852, poor pre-natal and post-partum women, infants, orphans, and foundlings (not eligible for orphanage care), were placed at Sister's of Charity Hospital. Some infants were found on doorsteps, alleyways, streets, and by-ways. Many of them were near death or already dead.

The hospital soon became over-crowded during the Cholera Epidemic in 1954, comprising the health of the already vulnerable women and infants. Three wood-frame cottages were erected on Edward Street and the women and infants were transferred.

In 1855, a three-story wing was erected, and by 1858, a four-story central building was erected. A lying-in hospital was its own department and it was under the charge of nine Sisters of Charity of St. Vincent de Paul. The third floor dormitory was utilized for the "creepers"; children one year and older. Infants from the age of two weeks to their first year were cared for in the second floor dormitory. A fire door was placed in the middle of the dormitory with a chute allowing for the evacuation in the event of a fire.

The population in August 1875, totaled 90 children; half being infants, and the other half were between the ages of three and five.

Generally, children remained at the asylum until the age of five. If a child's health was considered delicate, he or she would remain until six years of age. Infants were placed out for adoption. For those not adopted, boys were sent to St. Joseph's Asylum at the Limestone Institutions, and the girls were sent to St. Vincent's Female Orphan Asylum in Buffalo.

Mothers were expected to nurse their own infant at prescribed times along with another infant. Many infants died at St. Mary's due to their fragile condition. Women who were considered to be "unfortunate" (abused, erring, victims) were only allowed to utilize the accommodations of the asylum one time.

A measles epidemic ravaged the city for a three week period from February to the middle of March in 1891. Thirty-five cases were reported accompanied by eleven infant deaths between the ages of twenty-two days old and two and one half years of age.

In 1936, St. Mary's became one of twenty-eight agencies supported by the Catholic Charities.

The asylum had a dog, by the name of Teddy and he acted as the guard dog of the children. The children also had a summer home on Lake Shore Road at 18 Mile Creek.

Sophia Locher bequeathed her property at 125 Edward Street in 1941. The asylum utilized this for a boarding home for working females over the age of sixteen.

In 1943, the Sisters announced their plans to discontinue the maternity hospital at the Edward Street facility and to have it relocated to the prior Providence Retreat at 2157 Main Street. The Providence Retreat was first established in 1861 due to the inhumane treatment of the mentally ill who were placed in the poorhouse or jail.

Due to structural safety concerns, it became necessary for the asylum to be relocated. On September 13, 1946, the asylum moved to the former Sister's of Charity Hospital Site on Main and Florida Streets. The former surgical floors were remodeled and fireproof to accommodate their needs. The first floor housed three nurseries and two playrooms. The second floor housed three dormitories, five nursery rooms, and one playroom. Fifty infants were transferred from the Edward Street site, followed by another fifty from the summer home.