The small town rises on a rock, in a panoramic position overlooking the Biferno Valley, in an area where the Samnites already had their settlement 3000 years ago, as shown by remains of megalithic walls near the castle.
In nearby Rocca Aspromonte, presently a frazione of Castropignano, many important archeological pieces were found, such as a statue of goddess Minerva now kept in the Museum of Vienna, discovered in 1770. An ethimology of the name says that Castropignano derives from "Castrum expugnatum" and identifies it with the Samnite Palombino destroyed by the Romans in the third century AD.
In the Middle Ages the town was included in the County of Molise, then in 1345 the Norman D'Evoli family obtained the fiefdom, and kept it until the abolition of feudalism. The economy, based for centuries on agriculture and the movement of shepherds to Apulia along the nearby tratturo, fell into a deep crisis in the late 19th century, and the consequent emigration left the countryside abandoned.