The town (Latin Asisium, older Italian/Tuscan Ascesi or Scesi, no longer in use today) was colonized by the Romans in 399 BC and built in terraces on a rocky ridge on the west side of Monte Subasio. It was previously an acropolis of the Umbrians. The city walls, the forum (or market square Piazza del Comune), a theater, an amphitheater and the Temple of Minerva, which was later converted into the church of Santa Maria sopra Minerva, can still be found from Roman times. In 328 the town was Christianized by the current patron saint Rufino di Assisi (San Rufino).
In 545 the town was largely destroyed by the Ostrogoths, later came under the rule of the Lombards and was then placed under the control of the Dukes of Spoleto.
In the 12th century, Assisi became a free commune and adopted a Ghibelline orientation[6], which put it in opposition to the Guelph neighboring city of Perugia. Saint Francis of Assisi, who was born in Assisi in 1181/1182, was taken prisoner as a young man during these conflicts. In the 13th/14th century, the city expanded beyond the Roman city walls, and the walls were extended several times.
In the late Middle Ages, Assisi was under the changing rule of the popes, various condottieri, the dukes of Milan and Urbino, and finally returned to the Papal States in the 15th century.
The fact that Assisi was saved from fighting and thus possibly from destruction in 1944 is thanks to the then commander of the German occupation troops, Colonel Valentin Müller, who was able to persuade the German commander in Italy, Field Marshal Albert Kesselring, to declare Assisi an undefended, open hospital city. At the same time, Bishop Giuseppe Placido Nicolini and the Franciscan Rufino Niccacci, with helpers from the Catholic Church, organized the hiding of politically and racially persecuted people, including many Jews, in monasteries and other church buildings.