The first church on this site was built in 939, when Odo of Cluny was given the Roman palace of Alberic II of Spoleto, which was then converted into a Cluniac Benedictine monastery.

In 1760, the papal nephew and Grand Prior of the Knights, Cardinal Giovanni Battista Rezzonico, sought to improve the appearance of the buildings.

The reliefs on this facade, the entrance gate and the panels and stellae in the piazza include emblems and other references to the military and naval associations of the Knights of Malta and the Rezzonico family heraldry.

Piranesi provided the design, and Righi executed the great globe surrounded by putti in clouds, and Saint Basil in Glory supported by two angels.

The Grand Priory of Rome (a division of the Knights of Malta) with support from the Fondazione Roma financed the restoration of both the interior and exterior that lasted from 2015 to 2019.