Foligno railway station forms part of the main line from Rome to Ancona, and is the junction for Perugia; it is thus an important rail centre, with repair and maintenance yards for the trains of central Italy, and was therefore subjected to severe Allied aerial bombing in World War II, responsible for its relatively modern aspect, although it retains some medieval monuments.

After the war, the city's position in the plain and again its rail connections have led to a considerable suburban spread with the attendant problems of traffic and air pollution, as well as a severe encroachment on the Umbrian wetlands.

In the classic Roman age the city acquired importance first as a municipium, later as the seat of a prefecture and finally as a Statio principalis of road traffic along the ancient Via Flaminia.

The city began to decay in the late Roman Empire years: after the fall of the latter, Fulginiae became part of the Duchy of Spoleto, and was sacked by the Saracens in 881 and ruined by Magyars in 915 and again in 924: its inhabitants therefore decided to move, settling around the nearby Civitas Sancti Feliciani (former Castrum Sancti Feliciani), a church strengthened by walls where the Bishop and martyr Feliciano was buried in the 3rd century AD and which was then already populated.

The new seat had also attracted people from Forum Flaminii (now San Giovanni Profiamma), a neighbouring city and former bishopric that had been destroyed by the Lombards under Liutprand but remains a Latin Catholic titular see.

It changed hands often during the wars of the 13th century, until 1305 when it was seized from the Ghibelline Anastasi by the powerful Guelph family of the Trinci, acting as semi-independent deputies of the Holy See.

When Corrado Trinci turned against the Papal authority, Pope Eugene IV sent a force against Foligno in 1439, led by Cardinal Giovanni Vitelleschi.

Henceforth Foligno belonged to the Papal States until 1860, with the exception of the Napoleonic era, when it was part of the Roman Republic (1799) then of the French Empire (1809‑1814).