For the most part still surrounded by town walls dating back to the 16th century, the town of Città di Castello spreads out along the Tiber valley, on the spot where the Romans had founded the township of Tifernum Tiberinum.
The town may have been Etruscan; the Romans knew it as Tifernum Tiberinum ("Tifernum on the Tiber") or Civitas Tiberina. Just nearby, Pliny the Younger built his villa in Tuscis, which is identified with walls, mosaic floors and marble fragments surviving at a place now called Colle Plinio, the "Hill of Pliny".
In 550, Tifernum was largely destroyed during the Ostrogothic campaign by Fantalogus, at the orders ofTotila. The town was subsequently rebuilt by its bishop, Floridus, around a castle, and renamed first Castrum Felicitatis and later Civitas Castelli. By the Donation of Pepin of the Frankish king Pepin the Short in 752, it went to the Holy See, though in practice it was disputed between the papacy, Perugia and Florence. It was ruled by the Vitelli family, even after Cesare Borgia attached the city more directly to the Holy See.
In subsequent centuries, it had various rulers, among them Pier Saccone Tarlati di Pietramala, brother of Guido, Bishop of Arezzo. Pier Saccone sold it in 1322 to Guido Alberto de' Guidi di Modigliana. In the later Middle Ages it was governed successively by the Guelphs and Ghibellines. In 1375, Città di Castello joined the insurrection of other cities of the States of the Church. Cardinal Robert of Geneva (later antipope as Clement VII), tried to capture it using Breton mercenaries, but was repulsed. Under Pope Martin V in 1420, it was taken by the condottiero Braccio da Montone. Later Niccolò Vitelli, aided by Florence and Milan, became absolute ruler or tiranno. Antonio da Sangallo the Younger built an extensive palace for the Vitelli family.
In 1474, Sixtus IV sent his nephew, Cardinal Giuliano della Rovere (later Julius II); after fruitless negotiations he laid siege to the city, but Vitelli did not surrender until he learned that the command of the army had been given to Duke Federico III da Montefeltro. The following year Vitelli tried unsuccesefully to recapture the city; fear of Cesare Borgia induced him to desist, since Cesare Borgia had his father strangled and Città di Castello added to the papal possessions.
Towards the end of the twentieth century, the city has seen a considerable expansion northwards toward San Giustino, with industrial parks tracking the river, railroad and main highway: the area produces farm machinery, textiles, ceramics and furnishings.
After having been sacked and destroyed on the orders of Totila during the barbarian invasions, it was rebuilt under Bishop Florido and first took the name of Castrum Felicitatis and later, in the 10th century, that of Castrum Castelli.
It became a Comune during the late Middle Ages and was subjected to the rule of Perugia, to that of the Church and then to that of Florence; only in the 16th century, under Cesare Borgia, it definitely became dominion of the Papal State. Buildings which used to be the seat of administrative structures such as the Palace of the Podestà, with its baroque facade dating back to 1686, and the Town Hall, built in the Gothic style with an elegant portal and windows with two lights, testify to the ancient history of this Umbrian town. Traces of Gothic art are still to be found of the left-hand side of the Cathedral, which, having been constructed during the 11th century on the site of a Roman temple, was already radically modified in the middle of the 14th century.The churches of St.Dominic (1424), with its incomplete facade and ogival portal on the left-hand side, of St.Mary Maggiore, dating back to the Gothic era but adorned by a Renaissance facade, and finally that of St.Francis with its poligonal apses (1273), remodelled in the first years of the 18th century, complete the panorama of the town's religious buildings. The Municipal Pinacoteque contains works of art by Raffaello, Signorelli and Domenico Ghirlandaio, apart from others by Umbrian, Tuscan and Marche schools.