In 1871, the Sisters of Mercy converted a classroom at St. Bridget's School (724 N. 23rd) in St. Louis into a 25-bed infirmary for women and children. Two years later the facility became a general hospital — St. John’s Hospital.

In 1910, the Sisters secured a loan to construct a 200-bed facility at Euclid and Parkview overlooking Forest Park.  Even after expanding to 357 beds, adding OB, pediatrics and 24-hour emergency services, the need for beds and services continued.

In 1963, St. John's Mercy moved to its current location at Conway and Ballas.  In less than two years it was treating more than 71,000 patients annually, delivering 4,400 babies, and handling 47,000 outpatient and 17,000 emergency room cases. The burn center at St. John's Mercy (started in 1967) has become the largest of its kind in the state, treating children and adults from a two-state area.

To better describe the services and care available, St. John's Mercy Hospital became St. John's Mercy Medical Center on February 4, 1971. More recently, the Medical Center has embarked upon a long-term master facility plan that has already given rise to two new floors in the main hospital building, providing 66 private rooms for new mothers and two full-term nurseries. The David C. Pratt Cancer Center was opened in 2003, bringing the Medical Center's extensive oncology services together in one location. In 2006, the St. John's Mercy Heart Hospital became the region's first hospital dedicated to heart and vascular care.

And true to its beginnings, St. John's Mercy is still known for its care for mothers and babies. The Medical Center's 100-bed OB service, including a 27-bed neonatal intensive care unit, is recognized as a leader in the St. Louis area.