The Main Guard and the Chancellery were built in 1603 on order of Grand Master Alof de Wignacourt. The buildings face the Grand Master's Palace across Misraħ San Ġorġ. The central building served as the Guard Room of the Regimento di Guardia - the Grand Master's personal guards. It later served as the Main Guard to the British Governor. The building consists of a single floor on the front part and three floors on the rear onto Triq id-Dejqa owing to the differences in level between the streets.

In 1814 a portico was added in front of the entrance to the Guard Room. The portico is crowned by a stone sculpture of the British Royal Coat of Arms with lion and unicorn supporters. Below these carvings is an inscription in Latin dated 1814 recording Malta's request to become a British protectorate.

The building on the right, corner with Triq l-Arcisqof was the Order's Chancellery (Cancelleria) which housed the Order's archives.

The Chancellery building has a series of large windows set within a panel having slightly projecting sills and heavier cornices above the plain lintels. The Chancellery has a large hall which was decorated with ceiling frescos during the Vilhena grandmastership.

Mepa scheduled the Main Guard and the Cancelleria as a Grade 1 national monument as per Government Notice No. 276/08 in the Government Gazette dated March 28.