The Saint Mary together with the Belly River and Waterton River drains a small portion of Montana, in the United States, to the Hudson Bay watershed in Canada.

The river rises as a stream on Gunsight Mountain in Glacier National Park and flows into Gunsight Lake, then flows into Saint Mary Lake, exits the park and flows on into Lower St. Mary Lake in the Blackfeet Indian Reservation.

The St. Mary River Irrigation District (SMRID) is Canada’s largest irrigation district delivering water through 2,060 kilometres (1,280 mi) of canals and pipelines to approximately 1,505 square kilometres (372,000 acres) of land south of the Oldman and South Saskatchewan Rivers between Lethbridge and Medicine Hat.

In December 1945 the Canadian Pacific Railway transferred control of the projects to the government of Alberta, creating the St. Mary and Milk River Development (SMRD).

A dam was created in 1946 on the St. Mary River, to service the irrigation system, and water finally reached Medicine Hat in 1954 upon the completion of the St. Mary Main Canal.