The Sisters of St. Joseph came to Hamilton in 1852 to care for orphaned children. During another cholera epidemic among immigrants in 1854, they nursed the sick in the make-shift sheds set up by the Catholic church near the Great Western Railway depot on Stuart Street.
For the next 30 years, they built a reputation for caring for the ill and homeless poor. They received bequests to establish a hospital and finally in 1889 they decided to do it. A suitable location was found in "Undermount", a mansion originally built by Hamilton businessman, Mr. John Young and located at the corner of John Street South and Charlton Avenue. It was a large stone, three story building with a stone fence surrounding the grounds and an large iron gate. Despite some objections by the neighbours that a hospital would hurt their property values, St. Joseph's Hospital opened on June 11, 1890. The first floor was given over to administrative offices. The second and third floors were divided into wards and private rooms with space for 25 beds.
In 1894 they added St. Ann's Wing which increased the bed capacity to 55. It established a school of nursing in 1911 which graduated nurses until 1973 when the programme was transferred to Mohawk College. In 1916 they added a surgical wing. In 1923, they purchased the house at 58 Charlton Avenue East and converted it into a maternity hospital called Casa Maria.
The hospital went through a major reorganization and reconstruction to emerge as a modern medical facility in May 1947 occupying most of the block from Charlton and Mountain Boulevard. In 1958 Mountain Boulevard was renamed St. Joseph's Drive in its honour. Another major expansion occurred in 1962 with the completion of an 8 story hospital wing and 7 story nurses residence. Today it has grown into a 430-bed teaching hospital and a 30-bed chronic care unit.