Originally the town of Sant'Eufemia was known as Santa Femi. In the 14th century the town was renamed Santa Fumia and retained that name until 1863 when, by decree of King Victor Emmanuel II, it was named Sant'Eufemia a Maiella.
Until the 19th century Sant'Eufemia a Maiella was part of the Caramanico Terme. Then in 1064 Count Berardo gave the church of Sant'Eufemia and surrounding land at Caramanico to the Abbey of San Clemente a Casauria which retained possession of the town until 1145. In 1145, the area became the possession of Boemondo, who was the Count of Manoppello at the time. Eventually, in 1301 ownership was passed on to the Ughelli family and then to Giacomo Arcucci, the Count of Minervino. Upon the death of Giacomo Arcucci in 1389, it became the property of the D'Aquino family.