In 1877, the hospital first opened its doors to offer health care to the people of this town and its environs with a compliment of 206 beds. This was a legacy of the British, who once occupied the original structure as an army. The old barracks along with the adjoining lands were donated by the British government to the Government of Jamaica with specific instructions that the buildings should be used to house public health care services for the people of the town of Mandeville and its environs.

In 1938, 61 years later, the small hospital was expanded with the addition of tuberculosis wards. The new wards provided accommodation for and facilitated inpatient care of those suffering from the disease quite common during that period. In 1955, there was further development as the sum of Twenty Thousand pounds sterling was spent to build a new hospital to meet the health care needs of the growing population. Then came the fateful Kendal Train Crash which occurred just about eight miles or less away from Mandeville in 1957. This event played a pivotal role in further development and expansion of services at the hospital as, in response to the crash, the outpatient services which were up to that point offered offsite had to be relocated to the hospital grounds where the service has remained and well used ever since. As the social landscape of Jamaica changed, there was a growing desire among mothers to be, to have their births handled within the confines of a hospital. To satisfy this need, a maternity department with a compliment of 40 beds and 3 semi-private rooms was opened in 1964.

Four years later, there was still further expansion when a new floor was added to house medical and surgical wards and an operating theatre. Mandeville hospital was never quiet for too long, as over the years, the records show a continuous path of efforts to offer better service in better facilities, hence, there were always building projects interspersed with relatively brief periods of quietness. With the decade of the seventies came three major developments: in 1971, new modem x-ray equipment was added to improve diagnostic services; the outpatient department began to offer a wider range of services which comprised: surgery, medicine, ophthalmology, psychiatry, dermatology, dental care and dietetics. In 1978 the drug window services came on stream. In that same decade, in 1977 at the One Hundredth Anniversary of the hospital, a building fund was launched in a bid to have a paediatric ward added to the Hospital. In the mid 1980's, another new service was added when the Fertility Control Unit became functional. This service complimented the family planning efforts, which were offered in primary health care in the parish and exposed patients to new perspectives on planning their families.

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There were developments which benefited staff as well. This hospital has three sets of staff living facilities, one dormitory type nurses quarters which was the first one to be constructed and two sets of apartment buildings, Viking Hall and Viking Court facilities which provide more private and individualized accommodation for more members of staff. In 1997 under the National Health Sector rationalization progamme. The Mandeville hospital was redeveloped and refurbished at a cost of Seven Hundred Million dollars. In July, 2000, the new section of the hospital which stands as a showpiece and landmark in central Jamaica was completed and the services offered in the old Hospital were transferred to the new building that now exists. During this time, the Mandeville Public Hospital was upgraded and renamed Mandeville Regional Hospital. The official celebration and dedication ceremony of the redeveloped and refurbished hospital was held, April 3, 2001.