The hospital's colonial-style buildings were constructed in the late 1930s on 110,000 square metres (1,200,000 sq ft) of land.

During the Fall of Singapore in February 1942, it was the scene of a massacre by Japanese soldiers of wounded British servicemembers and medical staff.

[8] The family of late Mr Khoo Teck Puat had donated S$125 million for hospital construction and funding.

[9] JurongHealth ceased operations at Alexandra Hospital (AH) at 5.30 pm on 29 June 2015 to prepare for the opening of NTFGH the next day.

[13] The future hospital is planned to be pandemic-ready, green and sustainable, with phygital (seamlessly-integrated physical and digital) care, new roles for nurses and caregivers, under a resource-efficient Integrated General Hospital (IGH) model: "One patient, One bed, One care team, One principal doctor, One with the community, Healthcare" (OOOOOH).

[16] With a S$5 million gift from the Lien Foundation, the Center will conduct clinical trials and care for patients using nutrition, exercise, dietary supplements and repurposed drugs.

[16] Complementing the geroscience basic research at National University Health System led by Dr. Brian K. Kennedy, the Center's mission is to increase the Singapore population's healthspan by five years by slowing biological aging.

[16] Alexandra Hospital will form part of a future Health District in Queenstown[17] and with an increased clinical capacity, support the Healthier SG initiative.

[22] On 6 November 2019, a Therapeutic Horticulture Programme was started in the gardens to provide occupational therapy to patients.

[23] A commemorative plaque in the gardens honours the hundreds of hospitalized soldiers and staff massacred by Japanese forces in 1942.