After an outbreak of plague in 1522-4, the Società dei Forestieri (an association of ‘foreigners’ also known as the Compagnia di San Rocco) acquired a derelict church here that formed part of the adjacent Case di Santa Chiesa (Palazzo delle Sette).  Michele Sanmicheli, who was a prominent member of the association, obtained permission from Bishop Cardinal Nicolò Ridolfi for the construction of a new church on the site that would be dedicated to St Roch, the protector from plague.  It seems likely that Michele Sanmicheli designed the church.  

An oratory was fitted out in the Palazzo dei Sette in 1591, with a window that allowed services in San Rocco to be observed from the palace.

Although the portal is original, the rest of the façade was rebuilt in 1930.  It incorporates part of the original campanile (to the left of the small rose window) that houses two church bells.

The church is now deconsecrated.  It was restored by the Liceo d’Arte di Orvieto in 2007 (see below) and is sometimes open for exhibitions. 

Frescoes in the apse (ca. 1530)

These damaged frescoes on the wall of the apse depict:

1. ✴Christ in judgement with the Virgin and SS John the Baptist, Sebastian and Roch, in the lunette; and
   

2. ✴the Madonna and Child with SS Francis, Sebastian, Roch and Augustine, on the curved wall below.
   

This work is probably associated with two documents in the archives of Orvieto:

1. ✴one of 1527 in which an artist named Cristoforo Bartolomei da Marsciano undertook to paint an image of the Virgin and saints within two months; and
   

2. ✴another of 1534 in which the same artist requested payment from the heirs of Eusebio Gaspare di Montefiascone for paintings that he had executed in the apse of San Rocco.