The hospital was founded as the Royal South Hampshire Infirmary in 1835[1][2] and moved into its first premises in St Mary Street in 1838.

[1][5] In 1896, another new wing, containing a further two wards and some operating theatres, was started, as well as some cottages to house patients with infectious diseases and a mortuary.

[6] During World War II, a country home of Lord Mountbatten, the Broadlands, was used as an annexe for the hospital.

[3][5] As part of a transfer of mental health services from Knowle Hospital, a psychiatry block was completed in 1979.

[5] The hospital is heated as part of the Southampton District Energy Scheme network.