Although Umbran in origin, Assisi was influenced by the nearby Etruscan settlements.
Under the name Asisium, it became a flourishing Roman municipality. At the beginning of the 3rd century AD, the martyr Rufino, the first bishop of Assisi, introduced the Christian faith.
After the fall of the Roman Empire, Assisi was razed by Totila and the Goths (545 AD), recaptured by the Byzantines, conquered by the Lombards. Subject for a considerable period to the Duchy of Spoleto, it flourished again during the 11th and 12th centuries with the first experiments as an independent township, but soon it was troubled by wars. Subdued by Barbarossa, it was here that Federico II was educated. St. Francis and St. Claire were born here during this period (the former in 1181 or 1182, the latter in 1193 or 1194).
Besides imperial and papal dominion, Assisi was subject at various times to the Perugians, the Viscontis, the Montefeltros, the condottiere Braccio Fortebraccio, and the Sforzas. It was torn by feuds between the Upper and Lower parts of the town (Parte de Sopra and Parte de Sotto). From the 16th century to 1860, except for the brief Napoleonic period, it was part of the Papal States.