In 1226, the latter's sons Buonconte I and Taddeo da Montefeltro were appointed Counts of Urbino by emperor Frederick II.

Guido's successor, Federico I (1296–1322), increased his domains by taking Fano, Osimo, Recanati, Gubbio, Spoleto and Assisi from the Holy See.

Guidantonio (1403–1443) was appointed ruler of the Duchy of Spoleto by Pope Martin V (1419) and carried on war against Braccio da Montone with varying fortune.

The Urbinese then offered the lordship to Federico III (1444–1482), the illegitimate son of Guidantonio, a pupil of Vittorino da Feltre's school and a lover of art.

He adopted Francesco Maria della Rovere (1508–38), his sister's child, thus uniting the signoria of Sinigaglia with Urbino.

Pope Leo X deprived him of his territory, which was given to Lorenzo de' Medici, and later to Francesco Maria della Rovere.