One of the first civilisations in the area was the Opici, followed by the Etruscans, the Samnites and the Sidicini. The Samnites built fortifications on the hilltops, the remains of which are still visible on the hills of Montano, Caievola and Monteforte. The territory came under Roman control in 290 B.C., and the ruins of an old Roman bridge can be seen in a place called Frattelle.
Between the 6th and the 9th centuries A.D. Lombards invaded Vairano and built a fortress here, which was used to defend themselves against Saracen and other invasions. In the 11th century, the Normans subdued the Lombards, and in 1191 emperor Herny VI of Hohenstaufen gave the castle to Roffredo dell'Isola, the abbot of Montecassino.
The fortress underwent several transformations and reconstructions during centuries: the most important was made by Innico II d'Avalos Cacciapuoti in the 16th century. In 1590, Vairano and nearby Marzanello were bought by Baron Mormile who turned the military fortress into a residential seat. Mormile owned Vairano until 1806.
The historic meeting in 1860 between General Garibaldi and King Victor Emmanuel II, which led to the Italian Unification and the modern state of Italy, is said to have taken place in Vairano at Taverna della Catena.