Autonomous rule for the community of Cannobio and its valley came about in 1342, with the spontaneous submission to Luchino and Giovanni Visconti, lords of Milan.

Shortly after this apparition, a plague swept through the area devastating lakeside and valley towns and villages, but leaving Cannobio relatively unscathed.

Religious minds linked these two events and Cardinal Charles Borromeo ordered a chapel to be built to hold the painting which is still there today.

The opening of the lakeside road to the Swiss border in 1863 created favorable conditions for the arrival of factories, including silk mills.

In 1927 the territory of the comune of Cannobio was extended to incorporate some small villages in the vicinity (Traffiume, Sant’Agata, San Bartolomeo).

During the Second World War the people of Cannobio rose up against the Nazi and fascist regime, from 2 to 9 September 1944, and proclaimed the Republic of the Ossola.

The large lakefront piazza named after King Victor Emmanuel III was given a major refurbishment when in the winter of 2003–04 it was completely relaid in cobblestones and granite slabs.