The Sisters of Mercy organization was founded in Dublin, Ireland in 1831, by Catherine McAuley. A group of Sisters came to the United States under the direction of Sister Mary Joseph Lynch. In 1873 another group of Sisters came to Grand Rapids to teach at St. Andrews school. In 1879 Mother Mary Joseph Lynch, who worked in the Crimean War with Florence Nightingale, brought her group of Sisters to Big Rapids, Michigan. Mercy Hospital was started for the lumbermen and their families. Four Sisters, Mary Bertrand, Mary Baptist, Mary Anthony, and Sister Ignatius came from Big Rapids to start St. Mary's Hospital in 1893.

St. Mary's Hospital Training School of Nursing opened on June 7, 1898, under the guidance of Sister Mary Josephine Reck. In the early days of the school, an applicant could start the course during any month, but the preferred time was during May or September. The age requirement was flexible, young women between the ages of 20 and 30 years were eligible. A certificate of health from a respectable physician and character references were also required for entrance. A high school education was desired, but not required, since an eighth grade education was acceptable. The probationary period was six months. If the student demonstrated acceptable skills and attributes deemed essential in a nurse after that time, she was awarded the cap and was assigned the responsibilities of nursing care. The students worked twelve-hour days with one hour off on weekdays and two hours off on Sunday.

Mercy Central School of Nursing was organized in 1935 through the amalgamation of the schools of nursing of Mercy Hospital in Muskegon, Bay City, and [St. Mary’s Hospital] in Grand Rapids. By combining the three schools, finances were increased, clinical facilities were enlarged, and a better program for nurses training was created. A traditional three year diploma program continued until September 1953. At this time a revised curriculum was introduced. A great deal of time and effort was put forth by the faculty to review the old program. It was concluded that with improved methods of teaching, and better correlation of subject matter and practice nursing, a student could be prepared in a shorter period of time. The revised curriculum consisted of 27 months, at which time a student was eligible to write the state boards. Curriculum changes were an on-going procedure from this point, to ensure the very best possible education for the student. In 1965 Mercy Hospital, Bay City, withdrew from the amalgamation and in 1975, Mercy Hospital, Muskegon, also withdrew.

Mercy Central School of Nursing was approved by the Michigan Board of Nursing in 1935 and since 1942 was also accredited by the Accrediting Service of the National League of Nursing.

Mercy Central school of Nursing graduated its last class May 9, 1986. The nursing profession had reached a point where a four-year Baccalaureate program was recommended over the 21-month diploma program then being offered by MCSN.