The Cathedral stands on the site of previous sacred buildings of which the most ancient, an early Christian cathedral, probably stood on the current churchyard. The new cathedral, consecrated in 1075 by the Bishop Ulderico, was damaged a few years later in the earthquake of 1117. The construction of the current Cathedral was completed between the sixteenth and eighteenth centuries.
The winner of the contest that had been banned turned out to be Michelangelo, but the execution of the works was entrusted to the Istrian architect Andrea da Valle and to the architect Agostino Righetti who made substantial changes to the original project.
The Duomo was completed only in 1754 by the Venetian architect Girolamo Frigimelica, even if the grandiose façade, with three portals and two rose windows, designed by him, was never finished and later seriously damaged, together with the great dome, in the bombings of 1917 and 1918.

In the sacristy, undergraduates graduating in law, in the church the students of the other faculties, while "baccellierato" (grade that was conferred in the Middle Ages to the student who had achieved the first academic degree, lower than doctor), the "license" and the "degree" were conferred by the Bishop in the hall that is in the square, which still today bears, on the pediment of the door, three bull's heads, the famous University coat of arms. In the opposite square the "pig market" was held, but then when the square was given to the church, it was used as a cemetery and then became a lawn and later, in 1904, it was paved.
From Via Dietro Duomo you can see the three apses that end the central nave, the two terminal apses of the transept (the shorter nave), the bell tower, the dome with the high tambour and the large lantern.

The harmonious and luminous interior, reminiscent of that of S. Giustina, is a Latin cross with three naves divided by pillars. On the left, in the Chapel of the Madonna dei Ciechi, is a Madonna with child by Stefano dall'Arzere. Di Pietro Damini we can admire the second altar San Girolamo and the client Girolamo Selvatico and in the third chapel, the altarpiece depicting Jesus Crucified with the saints Maddalena and Caterina. At the side door is the cenotaph (honorary burial monument that does not contain the remains of the deceased) by Francesco Petrarca, who was the canon of the Duomo, a nineteenth-century work by Rinaldo Rinaldi. The sacristy of the Canonici conserves precious works of art including a Madonna with child by Giusto de 'Menabuoi, two panels with Santi di Giorgio Schiavone and two paintings by Giandomenico Tiepolo, depicting San Filippo Neri and San Girolamo Emiliani and a valuable Deposition by Jacopo Montagnana. Precious 15th-century reliquaries, including a gilded silver processional cross from 1228, a silver inkwell, a cross and two silver chandeliers and rock crystal from the 16th century are kept in the walnut-carved wardrobe of 1563. The presbytery, inaugurated in 1997 after some restoration works, is adorned with the statues of the Tuscan sculptor Giuliano Vangi. Once in the crypt we can admire the altar of San Daniele with bas-reliefs by Tiziano Aspetti (1565-1607). In the right transept, at the back, on the altar, the icon depicting the Madonna with the child that an ancient tradition wants belonged to the Petrarch who believed it had been painted by Giotto.
The basement of the Cathedral preserves mosaics, remains of columns, urns of terracotta, worked stone, bones of ox and horse, perhaps remains of ancient pagan sacrifices. Some Byzantine capitals with the inscription to the Goddess Fortuna are now in the Museo Civico agli Eremitani, other objects, such as stones, crosses, etc., are in the Diocesan Museum.