The conflict ensued after the end of the War of the League of Cambrai (1508–16), when Francesco Maria I della Rovere decided to take advantage of the situation to recover the Duchy of Urbino, from which he had been ousted in the previous year by troops of the Papal States.

Della Rovere set off with an army of some 5,000 infantry and 1,000 horses which he entrusted to Federico Gonzaga, lord of Bozzolo, reaching the walls of Urbino on 23 January 1517.

Pope Leo X reacted by hastily hiring an army of 10,000 troops under Lorenzo II de' Medici, Renzo da Ceri, Giulio Vitelli, and Guido Rangoni and sent it against Urbino.

The war was, however, ended by the lack of money of Francesco Maria della Rovere, who soon found himself unable to pay the troops hired at Verona.

In September they signed a treaty by which della Rovere was relieved of all ecclesiastical censures and was left free to retreat to Mantua with all his artillery, as well as the rich library collected in Urbino by the former duke Federico III da Montefeltro.