It is the burial place of the Spanish monarchs, Queen Isabella I and King Ferdinand, the Catholic Monarchs. Apart from these historical links, this building also contains a gallery of artworks and other items associated with Queen Isabella.

The Nasrid dynasty of Granada was the last Moorish dominion of Al-Andalus to fall in the Reconquista (Reconquest). This occurred in 1492 during the reign of the Catholic Monarchs, with the conquest of the city being an important stage of their combined reign.

On September 13, 1504, they declared that they wanted their remains to be taken to Granada, and to this effect a royal charter was issued at Medina del Campo, Castile-León, for the Royal Chapel to be built. The charter states:

First we ordain that in the Cathedral of the city of Granada it made an honest chapel in which are, when the will of Our Lord be, our bodies buried. This chapel will be called Of the Kings under the invocation of Saint John the Baptist and Saint John the Evangelist.

The Royal Chapel was built between 1505 and 1517 in Isabelline Gothic style and dedicated to St. John the Baptist and St. John the Evangelist, with the construction under the direction of Enrique Egas in Gothic style. Juan Gil de Hontañón, Juan de Badajoz the Elder and Lorenzo Vázquez de Segovia were also involved in the construction project.

The 16th century was the century of the greatest splendour of the Royal Chapel. Construction occurred during the lifetime of King Ferdinand, and the Chapel flourished under his successor Emperor Charles V, with the church decorated, and the supporting institution being enhanced.

Market Square in Front of the Sacristy and Doorway of the Cathedral of Granada in the 19th century, drawing by American Edwin Lord Weeks.

The late 18th and early 19th century brought difficulties to the institution. These were linked to political changes, economic difficulties and the profound change in church-state relations. The liberal regime ended with the Patronage regime and the original foundations of the institution becomes a fully ecclesiastical entity.

Some stability was brought about by the Concordat of 1851 which was followed by a Royal decree of reorganization of the Royal Chapels. Isabel II, who visited the Chapel in 1862, promoted a new organization. With the Restoration a new balance is achieved, which is manifested from the years of the fourth centenary of the capitulation of Granada and the discovery of the Americas. As a result of this renewal, this period also witnessed the first scientific publications on the chapel and its art collection.

During the 20th century there was growth in the historical and artistic, archival and musical aspects of the chapel. The museum was created by Royal decree in the year 1913. With the development of the tourist industry in Spain in the second half of 20th century, the Royal Chapel became one of the top tourist attractions of the city of Granada. Recently there has been a restoration with the collaboration of the Ministry of Culture of the Junta de Andalucía and the Foundation Caja Madrid, along with other public and private contributions.