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In 1855 a municipal sub-committee recommended the erection of a hospital in Port Elizabeth and thus a Provincial Committee for the Management of the Port Elizabeth Provincial Hospital came into being to guide its establishment in November 1855. While the building of the hospital was being undertaken, a temporary hospital was opened on 10 September 1856.

In 1856, Act No 5 for Regulating the Provincial Hospital at Port Elizabeth (CCP 6/2/1/1) was passed, which vested all control of the institution in a Board of Managers.

The completed hospital building was occupied in 1859 and the temporary hospital closed. By 1900 the need for a new hospital was realized and the foundation stone of this hospital was laid in 1912.

In terms of Ordinance No 5 of 1912 (Province of the Cape of Good Hope Official Gazette No 218, 27 January 1912), Hospital Districts were created in Divisional Council areas. Hospital Boards, named after the division or town in which the main hospital was situated, were constituted to control and manage all institutions under and created by them.