The first cathedral, dedicated to Saint Maurice, was built by Lidoire, Bishop of Toursfrom 337 to 371 (preceding Saint Martin). Burnt down in 561, it was restored by Gregory of Tours and rededicated in 590. Its location, at the south-west angle of the castrum, as well as its eastern orientation, resulted in the original access being through the late-Roman surrounding wall (such a configuration is quite rare).

The cathedral was then rebuilt as a Romanesque church during the second quarter of the 12th century but almost immediately burnt down again in 1166 during the conflict between Louis VII of France and Henry II of England (also count of Anjou, the adjacent region).

The present cathedral replaces the earlier 12th-century Romanesque building. The first phase concerned the south transept and the towers, as early as 1170. The chancel was rebuilt from 1236 to 1279 by Étienne de Mortagne but the nave took much longer to build. The architect Simon du Mans rebuilt the transept and started the nave, including six spans, aisle and chapel, built during the 14th century — the first two spans correspond to those of the old Romanesque cathedral and date back to the 12th century. The nave was only finished during the 15th century by architects Jean de Dammartin, Jean Papinand Jean Durand, thanks to the generosity of Charles VII and the Duke of Brittany Jean V.

During the construction of the present cathedral, the nave was extended westward and the towers surrounding its entrance were erected during the first half of the 16th century, the first tower in 1507 by Pierre de Valence 87 m high, and the second tower during 1534 and 1547 by Pierre Gadier. Highlighting the special feature of the building, called supra, the towers were erected outside of the old city. The late-Roman surrounding wall is visible in cross section at the rear of the towers from the north.