The first mention of Spoletium in history is the notice of the foundation of a colony there in 241 BC. (Liv. Epit. xx.; Yell. Pat. i. 14), and it was still, according to Cicero (Pro Balbo) colonia latina in primis firma et illustris: a Latin colony in 95 BC . After the battle of Trasimenus (217 BC) Spoletium was attacked by Hannibal, who was repulsed by the inhabitants (Liv. xxii. 9). During the Second Punic War the city was a useful ally to Rome. It suffered greatly during the civil wars of Marius and Sulla. The latter, after his victory over Crassus, confiscated the territory of Spoletium (82 BC.). From this time forth it was a municipium.
Under the empire it again became a flourishing town, but is not often mentioned in history. It was situated on a branch of the Via Flaminia, which left the main road at Narnia and rejoined it at Forum Flaminii. An ancient road also ran hence to Nursia. Martial speaks of its wine. Aemilianus, who had been proclaimed emperor by his soldiers in Moesia, was slain by them here on his way to Rome (253), after a reign of three or four months. Rescripts of Constantine (326) and Julian (362) are dated from Spoleto. The foundation of the episcopal see dates from the 4th century. Owing to its elevated position it was an important stronghold during the Vandal and Gothic wars; its walls were dismantled by Totila (Procop. Bell. got. iii. 12).
Under the Lombards, Spoleto became the capital of an independent duchy (from 570), and its dukes ruled a considerable part of central Italy. Together with other fiefs, it was bequeathed to Pope Gregory VII by the empress Matilda, but for some time struggled to maintain its independence. In 1155 it was destroyed by Frederick Barbarossa. In 1213 it was definitely occupied by Pope Gregory IX. During the absence of the papal court in Avignon, it was a prey to the struggles between Guelph and Ghibelline, until in 1354 Cardinal Gil Alvarez De Albornoz brought it once more under the authority of the Church.
In 1809 it became capital of the French department of Trasimene. In 1860 it was taken by the Italian troops after a gallant defence. Giovanni Pontano, founder of the Accademia Pontaniana of Naples, was born here.