The Picinisco origins are very old and there are traces of polygonal (cyclopean) walls. The area was inhabited by Samnites and later conquered by the Romans. It is assumed the existence of an already established village survived the Germanic and Saracen invasions.
Its history has always been linked to that of the neighbouring Atina since the Samnite period. In the Middle Ages the population left the valley and looked for shelter in the hills to escape the Barbarian invasions. In 1150 it is mentioned in a document of King Ruggero delimiting the boundaries of Atina.
Picinisco was involved in the struggles between the kings of the south and the papacy. The Angevin granted it to the various lords of the county of Alvito who kept it as a fiefdom until 1806. Due to its border locationit has experienced banditry in various eras.
In the nineteenth century there was an attempt to exploit the iron ore veins in the Canneto valley but the attempt failed due to for the poor quality of the ore. After the unification of Italy, much of the population emigrated in particular to England.
In World War II, the town was bombed and subjected to harassment and a further strong emigration depopulated the country.