After a devastating tornado ripped through Rochester in 1883, Mother Alfred Moes and the Sisters of Saint Francis proposed building a hospital to aid the sick and injured in Southern Minnesota — on the condition that William Worrall Mayo and his sons provide the medical service. They agreed, and in 1889 Saint Marys Hospital opened with 27 beds. It expanded continually over the years to meet the needs of the Mayo Clinic practice.
One of the hospital's largest expansion projects was the Mary Brigh Building additions in 1980. The addition added a 50-room surgical suite and more than 100 new intensive care beds to the hospital. In 1997, another major expansion was completed with the addition of more intensive care beds, an expanded Cardiac Laboratory and the Mayo Eugenio Litta Children's Hospital.
In 1986, Mayo Clinic, Rochester Methodist Hospital and Saint Marys Hospital integrated their operations under one governing board to more efficiently serve the needs of Mayo patients. As a part of that agreement, a special Sponsorship Board was created to ensure that the spiritual values integral to the hospital's history are perpetuated.