Historical evidence indicates that the first settlement near Settefrati was named Vicus and was founded by ancient Italic tribes, particularly the Samnites. The area was then taken over by the Romans in 253 BC. In the 5th century AD its name was changed to Settefrati.
From the beginning of the 4th century up to the 12 century, the territory was owned by the the Abbey of Montecassino and the Abbey of San Vincenzo. Over the centuries Settefrati suffered devasting invasions by the Visigoths, the Ostrogoths and Longobards and, between 881 and 916, there were numerous incursions by the Saracens.There is mention of the town in a document dating from 991 when the Abbot Monsone gives to Rainaldo, the Count of Marsi, the Church and Monastery of San Paolo located in Settefrati territory. Another document refers to the building of a stronghold or Castrum. This fortification was built by the Dukes of Aquino, at the hightest point of the town to protect the townspeople from further attack. Ownership of the town later passed to the Dukes of Cantelmo, Navarro and Gallio until the abolution of feudalism. In 1807 it became part of the Bourbon Kingdom of Naples.
In the fifteenth century Settefrati suffered numerous lootings and destruction by the Aragonese militia. From 1595, it became part of the possessions of the Gallio family and belonged to the duchy of Alvito. During the sixteenth century it was attacked, looted and set on fire by a band of brigands led by Marco Sciarra. In 1654 a violent earthquake almost completely destroyed the settlement. In 1656 it was temporarily abandoned due to an attack of the plague. After the unification of Italy in 1861, the area experienced the phenomenon of banditry and Settefrati was the refuge of the notorious brigand Domenico Coia, who was better known as Centrillo. He and his band of men had a hideaway in the rocky gorges of Canetto, which was located on the border between several different regions.
In the late 18th century and once again in the middle of the 19th century there were attempts to run ironworks near Settefrati and the mines in the Canetto valley, however in both events the experiment gave poor results. During the late 1800’s many of the poor peasant people from Settefrati began to emigrate in the hope of finding work and a better quality of life.
A huge earthquake hit this region in 1915. During the Second World War the town was invaded and occupied by German troops. Subquently the town was bombed by the Allied forces, and the population suffered severe hardship and deprivations. This lead to another wave of emigration after the war, with many people from Settefrati settling in Stamford Connecticut in the USA.
The town once again experienced significant damage during the earthquake of 1984, which had its epicenter in the neighbouring town of San Donato.