It is thought Gauls and Etruscans had some sort of presence here, though they left nothing behind to indicate permanent settlement. The Romans, on the other hand, left a deeper mark. The hill settlement of Bergamo is strategically placed on a lonely rise south of the Lombard pre-Alps between the Brembo and Serio river valleys and was no doubt appreciated not only as a trade centre but also as a handy lookout position over the vast Lombard plains to the south. As was typical in Roman settlements, the main roads were the intersecting decumanus (east–west road; Via Gombito) and cardo (north–south road; today Via Lupo and Via San Lorenzo).

Although Milan's skyscrapers to the southwest are visible on a clear day, historically Bergamo was more closely associated with Venice, which controlled the city for 350 years until Napoleon arrived. Medieval Bergamo was an industrious (textiles and metals) town that was incorporated into the Venetian empire in 1428, remaining under the domination of the Serenissima (Venetian Republic) until the latter's fall to Napoleon in 1797.