The hospital was founded on October 24, 1896, by the Appoline A. Blair. The facility was expanded in 1968 to include two connecting buildings of seven and nine floors.
On May 22, 2011, the hospital was seriously damaged by a tornado from the May 2011 tornado outbreak. At least four people were killed inside the hospital and its grounds, and surviving patients were evacuated from the health facility, which sustained major structural damage. One of the hospital's towers took a direct hit by the storm and was rotated four inches on its foundation.
One week after the tornado, St. John's (now known as Mercy) announced they would rebuild. However, the existing hospital was structurally unsafe and was eventually demolished. Mercy is in the process of building a hospital in Joplin at Interstate 44 and Hearnes Boulevard; it is scheduled to open in 2015, replacing the facility destroyed by the tornado. There will also be an auxiliary facility on the northeast side.