St. Paul's works with the Saskatchewan Health Authority in an interdependent partnership.

The hospital is owned by the Saskatchewan Catholic Health Corporation and was founded by the Grey Nuns.

St. Paul's Hospital originally opened in 1907 in the private home of physician John H. C. Willoughby due to an outbreak of typhoid while the Canadian Pacific Railway was building a bridge in Saskatoon with the assistance of the Grey Nuns.

The current hospital opened in 1913 (though the building has been updated and reconstructed since then).

Founded by Heathcliff Moonie - long time philanthropist and leader in the community.