Fermo, harmoniously arranged on the sides of “Sabùlo” Hill, Marche, was a place of settlement dating back to the Iron Age. According to G. Buti and G. Devoto, the transition of Picenum to  Iron Age is marked by new funeral rites of cremation, of proto-Villanovan type, characterized by the presence of “[…] urns shaped like a cylinder… We find a continuation of this type, very clearly proto-Villanovan, in the cremation tombs of  Fermo, which now is ascribed to the eighth century BC […]” (See G. Buti-G. Devoto, “Preistoria e Storia delle Regioni d’Italia” [“Prehistory and history of the Italy regions”], Florence, Sansoni, 1974, pp. 85-86 ).

After the conquest of  Picenum, around 268 BC, the Romans founded a colony of  Latin Law, "Firmum Picenum", around 264, from the territory of which oldest inscription of  Picenum has been handed down us (CIL I2, 383. See “XI International Congress of Greek and Latin Epigraphy”, Quasar, 1999, p. 396), and the etymology of which refers to concept of "firmum" or "stable", "sure," "strong", which presumably refers to its function as "fortified guard station" compared to the surrounding area. In conclusion, "Firmum" has been interpreted as "Castellum", i.e. as "fortified place": "Re et nomine 'Firmum'" (“'Strong' ['Firmum'] by its nature and in the name”), Liutprand (920 ca.-972) wrote about Fermo and its castle (See G. Fatteschi, “Memorie storico diplomatiche”, 1801, p. 182).

Fermo remained faithful to Rome with many important events of the war in which Rome was involved (the Second Punic War, Syrian and Social Wars); "Firmum firma fides Romanorum Colonia" ["'Fermo', the Roman colony and a city of strong faith "], the motto says of city). In Roman times it was then a town of considerable importance, with the right to mint its own coins. With the fall of Roman Empire, Fermo suffered numerous barbarian invasions and it was devastated by Alaric (458-507) and Athaulf (374 ca.-415) and also it suffered the raids of Attila (452 AD). In the sixth century it was also the center of Gothic War, and, in 533, it came under the dominion of Byzantines. In 569 the town came under Lombards, and administration of Duchy of Spoleto, even if, in eighth century, it was the seat of an independent Duchy. The eighth century was a period of significant changes to the city; arrival into Italy by Charlemagne (742-814) in defence of Pope Adrian I (died in 795) meant the end of Lombard Kingdom, and a subsequent submission, at least formally, to the Church State.

The ninth century was a relevant period for Fermo too; in fact, in 825, Lothair (795-855) made the city a very important center for the revival of studies in Italy. A "Schola", thus, was born in Fermo; then, in 1398, it became University at the behest of Pope Boniface IX (1356-1404). In the Middle Ages Fermo was a city of major importance; it was, in fact, the Chief-Town of  "Marca Fermana" as early as 920, with a large territory to administer. Still, in the eleventh century, it was attacked by the Normans, who were fought under the banner of the Church State; during the long struggle that opposed Empire and Papacy, Fermo sided with the Guelphs, followers of Pope, and, as a municipality, with other Italian cities, it revolted against the Empire; for this it was fiercely attacked by Frederick Barbarossa (1122-1190). For most of the thirteenth and fourteenth centuries the city was involved in bitter wars between Guelphs and Ghibellines, which coincided with the period of Holy See transfer to Avignon (1309-1377). With land-papal implemented by Cardinal Albornoz (1310-1367), Fermo was entrusted to the Visconti, but struggles for dominance of the city continued uninterrupted throughout the fourteenth century.

Pope Eugenius IV (1383-1447) appointed Francesco Sforza (1401-1466) Vicar of Fermo; the Sforza rule lasted until 1446, when it was overthrown by a popular revolt. In the sixteenth century, Fermo was subject to the Lordship of Oliverotto Uffreducci (died in 1503), who had fought, in the first instance, the orders of Cesare Borgia (1475-1507);  Oliverotto seized the city around 1502, with an energetic action which involved, according to the costumes of Italian tyrannies of the sixteenth century,  extermination of all possible claimants to the city government, settling later as Vicar of the Pope. Oliverotto Uffreducci, however, made a mistake that cost him the Vicariate and his life, because he participated in the so-called “Magione Conspiracy”, hatched against Cesare Borgia, who revenged himself making strangled him in prison. After the brief dominion of Cesare Borgia, and the subsequent attempt by a relative of Oliverotto to retake the city, Fermo, in 1520, returns to the Church State, under rule of which it will remain until the Unification of Italy (1861).