In the 3rd century after the peace of Constantine there were notable changes to the religious pagan cults who held their rituals in the originally Etruscan temples. The early Christian religious cults probably used these same temples. It is nearly certain that afterwards the first buildings of the Christian cult within the city walls, the urban parish church of Santa Maria and the church of Sant'Andrea, which have now disappeared, have been built on the ruins of a pagan temple. The church of Sant’Andrea in particular occupied the area where there is the Signorelli Theatre.
After the turmoil of the high Middle Ages, the occupation of the Goths, of the Byzantines and of the Longobards, while the city tried to organize itself as a free Comune, Cortona was divided into neighborhoods called Terzieri (since there were three of them). Each of these neighborhoods had a mother church. Today only faint traces remain of these mother churches.
- The Parish Church of Santa Maria, is the mother church of the terziere of Santa Maria. It was almost completely demolished in the 15th century to build the present cathedral. A few traces of the old church can be found on the facade.
- The Cathedral of San Vincenzo, the mother church of the terziere of San Vincenzo. Located outside the gateway of Sant'Agostino at 3, Via Duomo Vecchio, it was totally leveled in the 18th century. Private buildings now rise over the archaeological site, while sparse relics of the cathedral can be admired at the Etruscan Academy.
- The Church of San Marco, the mother church of the terziere of San Marco was also demolished in the 18th century and its title was transferred to the 1600's church located below it, which belonged to the Compagnia della Santissima Trinità and was called Church of San Marco starting from that moment. Although they are difficult to find, some of the remainders of the surrounding walls and facade can be seen at the end of Via San Marco, within the green archaeological zone, which is private property and is accessible at 39, Via San Marco.
In the 13th century, two other holy buildings were added to the three mother churches: the Church of San Francesco in 1240 which was meant to preserve the remains of its builder, Brother Elias, one of the pillars of the Franciscan history and, in 1297, the new Church of San Basilio. The Church of San Basilio was built in accordance with the projects by Pisano and was meant to protect Santa Margherita’s body from 1330 until today. In the following centuries other important holy buildings, more beautiful and rich in art work, many of which still preserve these works internally, were added to the two above mentioned churches.
CHURCH OF SAN FRANCESCO (13th century) Like the basilica of Saint Francis in Assisi, even this church was constructed by Brother Elias in 1247 on an area called Bagno della Regina, which had been donated to him by the Comune. Notable remains of some Roman constructions, probably hot springs, existed on that piece of land. The church is Gothic in style but has been heavily remodeled especially in the 17th century. The impact of its masses and the grace of its original lines, however, are still intact. The entry door and the large windows, which have recently been restored, are to be admired. Some manipulations concerned the painting on the walls, once embellished with famous frescoes, where Baroque altars have been placed. The large Gothic windows have been closed and the stone high altar has been replaced with a marble Baroque one created by Bernardino Radi (17th century), which contains a relic of the Holy Cross. Besides the Holy Cross, which was brought by Brother Elias from Constantinople, the church also preserves the tunic, an evangelistic manuscript, and a pillow. All these relics belonged to Saint Francis and have been preserved by Brother Elias, who called the saint "my mother", as we are told by Celano in the first biography of Saint Francis. On the wall on the right of the entrance there are the remains of a fresco attributed to Buffalmacco (16th century).
On the third altar there is the Immaculate Conception by Commodi (1609), while on the fourth the Miracle of the Mule by Cingoli (1597). In the chapel on the right of the apse there is a funerary monument dedicated to the first bishop of the diocese of Cortona, Ranieri Ubertini, who died in 1348. In the chorus we find the tomb of Brother Elias, the successor of Saint Francis as the leader of the order. In the third altar on the left wall there is a masterpiece by Pietro da Cortona (1597-1669): The Annunciation, one of the most beautiful paintings of the 17th century. Luca Signorelli was buried after his death in 1523 in the crypt below, which is no longer accessible as it was closed in the 17th century. The church and the monastery are still undergoing an extensive restoration work. Brother Dominic Basili, who is presently in charge of the complex, has written several publications about the history of the church and the life of Saint Francis and of his companion Elias, which can be read in this church.