After relocating several times, it finally settled at Sepoy Lines along Outram Road in 1882. The modern history of the SGH began on 29 March 1926 with a total of 800 beds housed in three hospital blocks. Today, only the distinctive clock tower of the original Bowyer Block remains – it has been gazetted as a national monument.

During World War Two, Japanese troops attacked the hospital on 14 February 1942 in retaliation against retreating Allied soldiers who fired at them from the hospital grounds. They killed an estimated 50 staff and patients that day and 150 more the following morning. In 1971, with the withdrawal of the British from Singapore, the local government took over the management of the hospital, and renamed and reopened it as a public hospital.

In 1998, the National Heritage Board declared Alexandra Hospital a historic site because of its services during the war. It was gazetted as a conserved building in 2014.

The hospital moved several times over the years, before shifting to its current location in Novena in 2000. Its site at Balestier-Serangoon was handed to the Cantonese community to build the Kwong Wai Shiu Hospital.

After transitioning into a general hospital, Tan Tock Seng Hospital has achieved many firsts in the fields of neurology, cardiology, rheumatology and geriatrics in Singapore. During the Severe Acute Respiratory Syndrome (SARS) outbreak in 2003, the hospital served as a quarantine facility to treat infected patients.

Pioneer leader Wong Ah Fook, who was the first president of the hospital, signed the Kwong Wai Shiu Free Hospital Ordinance in 1911, under which the old Tan Tock Seng hospital site on Serangoon Road was leased for 99 years at an annual rent of one dollar. The first three characters of the hospital’s name refers to the three Canton prefectures – Guangzhou (Kwong-Chau), Huizhou (Wai-Chau) and Zhaoqing (Shiu-Heng).

The hospital provided free outpatient services to the public and free hospitalisation to immigrants from Canton provinces. In 1911, it included inpatient, medical and maternity services comprising of both Western and Chinese medicine. Despite the difficulties of running a free hospital, it continued operating even during World War Two by collecting the bodies of war victims and conducting funeral services. The hospital continued to expand and improve its facilities, and in 1974, it opened its doors to all patients regardless of race, religion or dialect.