The church was originally built to meet the needs of Anglican worshippers among the civil population of Gibraltar, as the King's Chapel was primarily reserved for military use.

During the building process, the partially completed church had to be used for a short time as an emergency hospital during an epidemic of yellow fever.

In Gibraltar the money raised was used for the construction of new vestries and the creation of a second chapel in the south aisle of the cathedral, to be dedicated to Saint George and in memory of all who lost their lives in the Mediterranean area during the war.

The explosion of the RFA Bedenham on 27 April 1951 caused substantial damage to the cathedral, lifting the roof and smashing the stained glass.

As with most Church of England cathedrals, the priest in charge of the building and its ministry is called the Dean, currently Ian Tarrant (John Paddock retired in 2017).