St. Joseph's began as the Lowell Corporation Hospital, established in 1839 by area mill owners for the care of their employees.

On November 1, 1930, the deed of the hospital was transferred to the Archdiocese of Boston and placed under the direction of the Oblates with the Grey Nuns of the Cross of Ottawa acting as management.

Ultimately, the rapid growth and changing demographics of Lowell in the following decades created the need for additional hospitals.

The need for a health care facility to treat the people of Irish heritage was evident to Father John O'Brien, pastor of St. Patrick Parish (after whom Father John's Medicine is named) and Sister Emerentiana, Mother Superior of the Sisters of Charity of St. Vincent de Paul at St. Peter's Church.

When the two hospitals merged in 1992 to form Saints Memorial Medical Center, the organization became the Merrimack Valley's largest health care provider.