The discovered archaeological finds, which belonged to the end of the Bronze Era, testimony of a very antique settlement in this area, in particular on the Cavanero Mountain which dominates the present build-up area.

Around the II century A.D. the population started transferring to the left bank of the Pesio, in a strategic merchandising area, at the cross-point of the roman roads Emilia and Giulia. The legionaries established in this area a permanent garrison, called "Chiusa" to control the transit of goods and people, thus probably given the current name of "Chiusa" di Pesio.

With the decadency of the Roman Empire invasions, plunders and destructions followed one another, first by the Franks, then by the Saracens. The last ones influenced for a long time the popular imagination and are still the protagonists of numerous legends.

In 1000 the territory passed to the bishop of Asti, then to the rulers of Morozzo. Chiusa became a municipality during the first years of the XIII century and sworn allegiance to the Marquis of Ceva, Angevin vassal.

The municipality was included among the dominium of the Solaro di Moretta with the Savoy ascent and passed then under direct control of the House of Savoy.

Heavy plunders and predations invested Chiusa di Pesio with the arrival of the French and Spanish troops the first half of the eighteenth-century and some years later with the arrival of the Napoleonic troops. It was also during those years that the municipality underwent an economical revolution. The presence of woods, the energy from the Pesio stream and the activity of the inhabitants created the condition for the rise of numerous industries like spinning mills, factories for lime,  for tannin mining, for ceramic processing and the famous Glass and Ceramic Factory Organisation. This industrial development was the origin of a strong demographic increase, which reached 8000 inhabitants at the end of the XIX century. The agricultural and craftworks sectors grew parallel.

The twentieth-century was a crisis century for Chiusa di Pesio instead, with a remarkable diminishing of the population due to the two world wars and the consequent economical worsening conditions, phenomenon which induced a great part of the population to leave Chiusa.

However there were also some particularly important events linked to the partisan resistance of the Pesio Valley, which offered a national relief to the town. Nowadays this memory crack is remembered in the local resistance museum.