Operated by Trinity Health, it was founded in 1907 by the Sisters of Saint Joseph of Chambéry and is designated as a Level II trauma center.

Saint Mary's has been a teaching hospital for the Yale University School of Medicine for over 40 years.

[5] In July 2014 Tenet Healthcare announced that the hospital would be acquired by a Tenet subsidiary, with the hospital's religious directives and uncompensated care policies remaining intact.

[7] In September 2015, Saint Mary's Hospital was acquired by Livonia, Michigan-based Trinity Health, who had recently acquired Saint Francis Hospital & Medical Center in Hartford.

[8] In 2018, Trinity Health opened a center for multiple sclerosis treatment and research at the hospital.