Ascoli was founded by an Italic population (Piceni) several centuries before Rome's founding on the important Via Salaria, the salt road that connected Latium with the salt production areas on the Adriatic coast. In 268 BC it became acivitas foederata, a "federated" city with nominal independence from Rome. In 91 BC, together with other cities in central Italy, it revolted against Rome, but in 89 BC was reconquered and destroyed by Pompeius Strabo. Its inhabitants acquired Roman citizenship, following the developments and the eventual fall of the Roman Empire.
During the Middle Ages Ascoli was ravaged by the Ostrogoths and then by the Lombards of King Faroald (578). After nearly two centuries as part of the Lombard Duchy of Spoleto (593-789), Ascoli was ruled by the Franks through their vicars, but ultimately it was the bishops that gained influence and power over the city.
In 1189 a free republican municipality was established but internal strife led dramatically to the demise of civic values and freedom and to unfortunate ventures against neighboring enemies. This unstable situation opened the way to foreign dictatorships, like those of Galeotto I Malatesta (14th century), initially recruited as a mercenary (condottiero) in the war against Fermo, and Francesco Sforza. Sforza was ousted in 1482, but Ascoli was again compelled to submit to the Papal suzerainty. In 1860 it was annexed, together with Marche and Umbria, into the newly unified Kingdom of Italy.
The central historical part of the city is built in marble called travertino, a grey-hued stone extracted from the surrounding mountains. Its central Renaissance square, Piazza del Popolo ("Square of the People") is considered one of the most beautiful in Italy. According to traditional accounts, Ascoli Piceno was home to more than two hundred towers in the Middle Ages: today some fifty can still be seen.