Santa Maria in Campitelli is located over the former site of the Temple of Jupiter Stator, part of the Porticus Octaviae until the area's destruction in the Great Fire of Rome in the mid-1st century.

[2] Circa 1656, the city of Rome was ravaged by plague, and it was felt that the prayers to this icon, which had been carried in procession through the streets, had played a role in stopping the epidemic.

This putative miraculous intervention prompted Pope Alexander VII to erect a grander church, instead of the ancient oratory, to house the icon.

The main altar of the church houses the icon in a gilded glory or gloria of angels, clouds and rays of light, recalls the effects used by Bernini for the apse of Basilica of St Peter.

Since the time of the James Francis Edward Stuart, the church has been a center of devotion praying for the conversion of England back to Catholicism.