SGH had its beginnings in 1821, when the first General Hospital was located in the cantonment for troops near the Singapore River. It later shifted to Pearl's Bank and then to the Kandang Kerbau district, before finally settling at Sepoy Lines in Outram Road in 1882.

The modern history of SGH began on 29 March 1926, with the opening of 800 beds in the Bowyer, Stanley and Norris Blocks. Today, only the Bowyer Block with its distinctive clock tower remains.

In 1981, the Hospital was rebuilt, with its current 8-block complex housing inpatient wards, ambulatory and support services, research laboratories and a postgraduate medical institute.

On 1 April 1989, the Hospital was restructured, paving the way for a more responsive organisation geared to cope with the rapid pace of change in healthcare services and patient expectations for better service. As a restructured hospital, SGH is still 100 per cent government-owned and is a not-for-profit institution. More than 60 per cent of our beds are allocated for subsidised patients, giving them access to a good standard of affordable healthcare.

On 31 March 2000, following a major reorganisation of the public sector healthcare services initiated by the Ministry of Health, SGH came under the management of Singapore Health Services or SingHealth. The SingHealth Group is positioned to serve the eastern sector of Singapore through a cluster network of 4 hospitals, 5 specialist centres and 7 polyclinics.