In 1917, Misericordia General Hospital (MGH) was created to serve the growing surgical and health care needs of its surrounding neighbourhoods of Wolseley, River Heights, Crescentwood, and Fort Rouge in Winnipeg, Manitoba. Like its predecessor, Winnipeg Maternity Hospital, MGH was owned and founded by the Misericordia Sisters whose motherhouse was in Montreal. Throughout its existence, The Misericordia Sisters continued to be active in the operations of MGH. Over 45 sisters were involved throughout the 1950s, for example.

In 1917, MGH had 125 beds, fifty bassinets, and fifty medical practitioners. An additional 100 beds were added in 1927. With the addition of the Maryland Wing in 1950, the total number of beds became 305. In 1954, as construction began on the Cornish and Wolseley West additions, a total number of 418 beds and 60 bassinets were accommodated, and a full range of diagnostic services were available.

In 1922, MGH was awarded a Grade “A” facility approval from the Catholic Association of Federated Hospitals and the American College of Surgeons.

In 1971, a new Emergency Department and Intensive Care Unit was added in the newly constructed Riverview Annex.

In 1993, Eye Care Centre of Excellence was consolidated and established at MGH, while pediatrics and Inpatient Psychiatry were removed from MGH’s purview, along with the Obstetrics Department in 1997.

In 1998, MGH's emergency room was closed, and it was re-established as the Misericordia Health Centre, which served as an urgent care centre, and houses a diverse range of health-care programs.