Prior to the establishment of a quarantine facility at Moulmein Road, there existed a quarantine camp at Balestier in 1907. Opened in 1913, the quarantine facility at Moulmein Road was initially known as the Isolation Hospital. It was later renamed to the Middleton Hospital in 1920, in recognition of Dr. W.R.C Middleton, who had served the hospital for 27 years, upon his retirement. The centre became a branch of Tan Tock Seng Hospital (TTSH) in 1985, was renamed the Communicable Disease Centre (CDC), and came under the management of the National Healthcare Group. On 1 April 1995, it came under TTSH's direct administration.
