It is located in the Apennines bordering Umbria, between the valleys of the rivers Potenza and Chienti, about 64 kilometres (40 mi) from Ancona.

Later it appears as a dependent autonomous community with the foedus aequum, an "equal" treaty with Rome (Mommsen, Römisches Staatsrecht, iii.

Boniface III of Tuscany occupied the duchy around 1050, and then ceded it to his daughter Matilda, who in turn donated it to the Papal States.

Initially Ghibelline, it later became a Guelph stronghold and suffered much under Emperor Frederick II on account of its loyalty to the pope; Manfred of Sicily's troops, led by Percivalle Doria, besieged and destroyed it (1256): much of the population was killed, but Camerino recovered under Gentile Da Varano, who was amongst the refugees that returned in 1262.

Giulio Cesare's daughter, Camilla Battista da Varano, was canonized a saint by Pope Benedict XVI in 2010.