This hospital was founded on 13 March 1848. Its founders, who were predominately Quakers, recognised the needs of people suffering from diseases of the heart and lungs, particularly pulmonary tuberculosis, who were not able to afford adequate medical attention. Their institution was intended to offer the same advantages as the Brompton Hospital (established in 1842) conferred on the western portion of the Metropolis whilst the Royal Chest Hospital, City Road, (founded 1814), was perceived as too small to accommodate the growing number of patients in the north and east of London seeking care.
As the City of London Hospital for Diseases of the Chest, the voluntary hospital began life in 1848 as a public dispensary, offering out-patient care only in Liverpool Street. Plans were soon drawn up for a new hospital and a site was obtained through the lease of crown property at Bonners Fields, Victoria Park, East London. In 1851 the foundation stone was laid by Prince Albert, who together with Queen Victoria, contributed towards the building costs of thirty thousand pounds. The new Hospital, designed by Mr Ordish, opened in 1855 and was soon able to provide 80 beds. By 1881 the original design had been completed to provide 164 beds and was one of the first to employ the corridor system. Patients were admitted on governors' recommendation and were asked to contribute towards the cost of their care
With the development of the open air treatment for TB, balconies were added to the building in 1900 and the Hospital opened its own Sanatorium for women and children at Saunderton in Buckinghamshire. In 1923 its name was changed to the City of London Hospital for Diseases of the Heart and Lungs before changing again in 1937 to the London Chest Hospital. A Pathological Laboratory & Research Institute opened in 1927 through the support of the Prudential Assurance Company and in 1937 a new Surgical Wing was added to the Hospital. The Hospital was badly damaged by bombing during the Second World War, but remained open through public generosity allowing repairs to be carried out.
The London Chest became part of the National Health Service in 1948 and was designated as a teaching hospital in accordance with Part III of the third schedule of the Act. It was linked with the Brompton as one teaching hospital and the Board of Governors was reconstituted to cover both hospitals and its membership was increased from 20 to 30 members (for minutes see Royal Brompton Hospital). The Hospital became part of a Special Health Authority: the National Chest and Heart Hospitals (with the National Heart, the Brompton and Frimley hospitals) in 1974. The Hospital expanded its work to take in 4 chest clinics in East London and its cardio thoracic surgery also grew with the opening of new theatres and intensive care facilities during the 1980's. In 1988 the hospital shared in the award of a 'Royal' title to the Brompton Group. In line with government recommendations following the publication of the Tomlinson Report in 1982 the Hospital joined with St. Bartholomew's and the Royal London Hospitals to form the Royal Hospitals NHS Trust in April 1994.