The first settlements around Vezzano began in prehistoric times, by the so-called Liguri-Apuani. We don't have much material from that period; the first official document naming Vezzano bears the date 19th of May 963, and was written by Emperor Otto I to assign Vezzano castle and its palace to the bishop of Luni. Until XIII century the episcopal influence on Vezzano remained strong, although the family Da Vezzano tried many times to size the power.

In 1276 the fights between the bishops and the noble families were stifled because Genoa, interested in the Vezzano's strategic position, extended its dominion over the village. During the Renaissance Vezzano knew a period of peace and prosperity; the little town was enlarged and new buildings were erected.

On the other hand, the XVI century was a period of decline, as the Genoese started being interested in the valley, rather than in the hills, for their trades. Under the French domination, Vezzano didn't manage to regain its prestige, although the new masters valued the town for its strategic position. After the Vienna Congress, Vezzano was annexed to the Regno di Sardegna along with all nearby territories, to then become part of the Regno d'Italia.