The origins of this village date back to when the Greeks colonized the valley of Basento between the fifth and sixth century BC that led to the foundation of an urban center called Maudoro, or "world of gold". In the tenth century, because of the Saracen invasions, the inhabitants moved to what we know today as Castelmezzano.

It was occupied by the Lombards and later by the Normans, who built a castle called "Castrum Medianum", which stands for "middle castle". It was so named because it was built between the castles of Pietrapertosae Albano, from which derives the original name of the city.

Castelmezzano, also dominated by the Angevins, experienced difficult periods and in 1310, it was acquired by the Diocese of Potenza and later by that of Acerenza. The Aragonese conquered it between the fourteenth and sixteenth centuries and gave many landowners, parts of the city as a fief.

It was ruled by the De Leonardis family for about a century between 1500. In the nineteenth century when it was under the rule of the De Lerma family, it was the victim of the plague of brigandage and at the end of the century many moved overseas.