The Sisters of St. Joseph Health System traces its beginnings to Le Puy, France, in 1651, with the founding of the Congregation of the Sisters of St. Joseph. The Sisters trace their origin to and follow the spirit of the foundation made by Jean Pierre Medaille. Their first charge: running the orphanage in Le Puy. Soon they were engaged throughout France in running schools, hospitals, orphanages, and institutes for the deaf.

The congregation survived the French Revolution, and in 1836 eight Sisters traveled to New Orleans to launch their first mission in America. In 1889 eleven Sisters arrived in Kalamazoo, Michigan, at the request of the Diocese of Detroit for the purpose of establishing a hospital. At about the same time, under the leadership of Mother Margaret Mary Lacy these same Sisters began an orphanage and a school. The Sisters of St. Joseph of Nazareth established their motherhouse at Nazareth, on the outskirts of the city, from which they conducted their health care ministry as well as their ministries in social work, education, parish ministry, spiritual development and pastoral ministry.

By 1999, the year the Sisters joined their health ministry with that of the Daughters of Charity, the Sisters of St. Joseph Health System had grown to encompass four regional health systems operating more than 30 hospitals, nursing homes, outpatient clinics, and other health care facilities spread throughout lower Michigan.