The Chantry Chapel of St James was built in 1126 by Roger de Newburgh, 2nd Norman Earl of Warwick. In the late 14th century it was rebuilt by the 12th Earl of Warwick. He granted the benefice of the Chapel to the Guild of St George, a guild created on 20 April 1383 under licence from King Richard II. The Guild of St George was later joined there by the Guild of the Blessed Virgin, which had been based at the Collegiate Church of St Mary, forming the United Guilds of Warwick. Living quarters and reception, meeting, and dining halls were added to the chapel as a consequence. The Guildhall was built in 1450 by the 16th Earl of Warwick.

In 1545 the hospital took on a new task, that of housing what is now Warwick School - the oldest boys school in the country. Even though only a few years were spent here, a couple of notable schoolmasters were present; perhaps marking the beginning of the curve that made it what it is today - one of the most successful schools in the country.

The United Guilds were dispersed by King Henry VIII in 1546. However, their property had already been transferred to the Burgesses of Warwick by Thomas Oken, Master of the Guilds. The 1st Earl of Leicester acquired the buildings in 1571, founding therein a hospital for aged or injured soldiers and their wives, under royal charter from Queen Elizabeth I, run by 12 resident "Brethren" (originally soldiers) under the charge of a "Master", and funded from the income of various estates. This lasted until 1950. Between 1881 and 1930 the hospital served as a terminus for the Leamington & Warwick Tramways & Omnibus Company, the other end being close to Leamington Spa railway station.

In 1956 the Corporation of the Master and Brethren of the Hospital was abolished by Act of Parliament, having operated under the original charter for nearly 400 years, and replaced with a board of Governors. On 3 November 1966 a restored Hospital with modernised quarters was opened by Queen Elizabeth the Queen Mother, and today the Hospital is run by the Master, a retired officer of the Armed Forces. Eight ex-servicemen and their wives are provided with flats in return for their past services. The Hospital is funded by visitor income, the original estates having been sold over the years.

Other historical notes of interest:

The Grade I listed stone urn in the Master's Garden is 2,000 years old and was originally part of an Egyptian nilometer.
A banquet held for King James I at the Great Hall put the town of Warwick into debt for ten years.