Map showing the location of the Campione enclave near the centre.
In the first century BC the Romans founded the garrison town of Campilonum to protect their territories from Helvetii invasions.
Toto of Campione, a local Lombard lord, left his inheritance to the archbishopric of Milan. Ownership was transferred to the abbey of Sant’Ambrogio. In 1512, the surrounding area of Ticino was transferred from the ownership of the bishop of Como to Switzerland by Pope Julius II, as thanks for support in the War of the Holy League. However, the abbey maintained control over what is now Campione d'Italia and some territory on the western bank of Lake Lugano.
When Ticino chose to become part of the Swiss Confederation in 1798, the people of Campione chose to remain part of Lombardy. In 1800, Ticino proposed exchanging Indemini for Campione. In 1814 a referendum was held, and the residents of Campione opposed it. In 1848, during the wars of Italian unification, Campione petitioned Switzerland for annexation. This was rejected due to the Swiss desire for neutrality.
After Italian unification in 1861, all land west of Lake Lugano and half of the lake were given to Switzerland so that Swiss trade and transport would not have to pass through Italy. The d'Italia was added to the name of Campione in the 1930s by Prime Minister Benito Mussolini and an ornamental gate to the city was built. This was to assert the exclave's Italian-ness.
During World War II, the US Office of Strategic Services (OSS – the precursor to the CIA) — partly through Berne OSS chief Allen Welsh Dulles — maintained a unit in Campione for operations in Italy. At the time the Italian fascist regime did not have control over the exclave. The Swiss ignored the situation as long as the Americans kept a low profile. Postage stamps were issued during this period inscribed "Campione d'Italia" and valued in Swiss currency.