The South Saskatchewan Hospital Centre was established on 15 February 1967 by an Act of the provincial legislature. The Board of Governors held its inaugural meeting on 9 March 1967, and was assigned the task of developing a health complex with comprehensive services for Southern Saskatchewan. In addition, the objectives of the SSHC were: to participate in the improvement of the general health of the community; to establish and maintain medical referral and teaching hospitals for residents of Regina and Southern Saskatchewan; to provide training and continuing education for health care personnel; to encourage research in the health field; to provide facilities for health services operated by voluntary and government health agencies; and to develop and promote improved standards of hospital administration and health care delivery.

On 1 April 1968, the Wascana Hospital - an amalgamation of the former Physical Restoration Centre and the Regina Geriatric Centre - became the first operating division of the SSCH. The facility provided comprehensive rehabilitation and chronic care services to the residents of Southern Saskatchewan, as well as provided beds, facilities and treatment for veterans and the Workers Compensation Board. Wascana remained a division of the SSCH until 1986 when control of the facility was transferred to the newly established Wascana Rehabilitation Centre Board. A second active facility came under the auspices of the SSHC when the Provincial Government purchased the Regina Grey Nuns' Hospital from the Sisters of Charity (Grey Nuns) of Regina on 31 August 1972. On 1 September 1973, the hospital was renamed the Pasqua Hospital. This acute care facility also housed the Allan Blair Memorial Clinic (Cancer) operated by the Saskatchewan Cancer Commission.

The SSHC devoted seven years to the planning and construction of the Plains Health Centre before it was opened in 1974. The new 303-bed facility provided the services of medicine, general surgery, orthopaedics, neurological science, urology, plastic surgery, ICU/CCU and self-care; carried out all cardio-vascular surgery; provided a centre for severe multiple trauma; provided resource services to rural hospitals in the south-east region of Saskatchewan; was a teaching centre for medical, nursing, and para-medical personnel; and included research within the health field in its programs. The hospital was affiliated with the College of Medicine at the University of Saskatchewan.

The South Saskatchewan Hospital Centre ceased to exist in 1992 when the Regina District Health Board (14 February 1992) and the Regina Health District (May 1993) were established. The facilities under SSHC control and all their assets were given over to the new Board and administration. The following individuals have served as Executive Director of the SSHC: F. Lloyd Mussells, MD (1967-1970), Eugene F. Bourassa (1971-1973), and Harvey H. Fox (1974-1992).