The adjective Grande distinguishes this church from the San Simeone Piccolo, which was smaller in size until its 18th-century reconstruction.

Originally a modest building of wood, after a fire in 1150, it was rebuilt in stone and made parish church.

The Napoleonic government joined the parish to that of San Simeone Piccolo The interior floor appears to have been raised after burials were pursued here during the plague of 1630.

Inside, to the right of the entrance, is a Presentation at the Temple with portraits of donors by Jacopo Palma the Younger.

The Annunciation, previously attributed to Palma the Younger is today recognized as a work of the painter Blanc.