The Museum, opened to the public in 1981, is housed in the sixteenth-century Palazzo Panichi overlooking Piazza Arringo in the historic center of Ascoli Piceno. The Museum is divided into three sections with a chronological path that winds through the three floors of the palace. Through the artifacts of the rich civic collection of Ascoli, created in 1865 based on the eighteenth-century donation of Bishop Mazzoni, and the findings from recent excavations, it offers an extraordinary archaeological overview of the Ascoli territory and highlights the peculiar characteristics of southern Piceno.

The visit path begins on the second floor where artifacts from prehistoric complexes from the Paleolithic to the Bronze Age are exhibited. Particularly interesting is the exhibition dedicated, on the first floor, to the artifacts from the Picene age complexes, which illustrate the plurality and peculiarity of the cultural aspects of this territory in the 1st millennium BC. The ground floor, which also includes remains of ancient wall structures museumized on-site, houses artifacts from the Roman era. The museum path is completed with a visit to the nearby equipped area on the ground floor of Palazzo dei Capitani, overlooking the beautiful Piazza del Popolo, and with a visit to the Roman monuments still visible, such as the Theater and the Porta Gemina, in some cases also incorporated into later structures as in the case of the Temple whose structures are readable in the perimeter walls of the Church of San Venanzio.