The College of Physicians and Surgeons of the Province of Saskatchewan was established in 1906 as a corporate body under The Medical Profession Act (S.S. 1906, c. 28) to administer and oversee the registration, licensing and discipline of medical practitioners in Saskatchewan. All members in good standing of the College of Physicians and Surgeons of the North-West Territories were registered under the provisions of the new College. The College's first registrar was appointed by the Lieutenant Governor of Saskatchewan. A council of the College was comprised of one elected member from seven electoral districts within the province. Within the council, members annually elected a president, vice-president and an executive committee of at least three members. The council was responsible for the appointment of the registrar and of other members to carry out, through various committees, the provisions of the Act.

In January 1934, a special legislative committee appointed by the College of Physicians and Surgeons of Saskatchewan and the Saskatchewan Medical Association examined the possibility of a merger between the two bodies for the purposes of conducting business with governments and professional bodies in other jurisdictions. The two bodies merged in September 1936 and adopted the name of the College of Physicians and Surgeons of Saskatchewan; however, the former Saskatchewan Medical Association was renamed the Saskatchewan Division, Canadian Medical Association. Internally, each body maintained distinct and separate organizational structures, though many members served on committees for both. By the mid-1960s, the Saskatchewan Division looked to re-organize into an independent body and in October 1966, delegates at its annual meeting adopted a resolution to re-establish the Saskatchewan Medical Association.

The College of Physicians and Surgeons of Saskatchewan continues (2012) as a self-regulating body responsible for the licensing and discipline of medical
practitioners and for developing and ensuring the standards of medical practice in Saskatchewan. Its council consists of twelve elected physicians, five non-medical members and the Dean of Medicine of the University of Saskatchewan or his/her designate. An executive committee is comprised of a president, vice-president, one non-medical member and two members elected at large. Members also serve on various committees established through the College's bylaws. The College's head office is located in Saskatoon.