His headquarters, originally located in the royal palace, was moved in 1856 to the University of Cagliari building, following the donation of collections made to this institution by King Carlo Felice. At the beginning of the twentieth century, the museum, rapidly expanding, needed a different location.
The inauguration of the new structure, located in Independence Square and designed by Dionigi Scano, took place in 1904, with the exhibition setup curated by Antonio Taramelli, a distinguished archaeologist and superintendent from 1901 to 1931. Since 1993, the museum, having significantly enriched through private donations and materials from excavations, has moved to the current prestigious headquarters of the Citadel of Museums, a multifunctional cultural facility designed by architects Piero Gazzola and Libero Cecchini in the area of the eighteenth-century Royal Arsenal.
The museum offers the possibility to undertake a complete chronological journey through the prehistory and ancient history of Sardinia through an exhibition path arranged over four floors. In the basement, artifacts are displayed according to a chronological-didactic criterion, illustrating all the cultural phases that followed on the island from the Early Neolithic (around 6000-4000 BC) to the Early Middle Ages (8th century AD).
On the other floors, the display of materials follows a topographical criterion with the illustration of the main archaeological sites present in the central-southern territory of Sardinia. Five fundamental cultural moments are highlighted: the pre-Nuragic age, with artifacts from the Neolithic and Eneolithic period (6000-1800 BC) and the early Bronze Age (1800-1600 BC), the Nuragic period, illustrated by materials dating from the Middle Bronze Age (1600-1300 BC) to the second Iron Age (600 BC), the Phoenician-Punic period (second half of the 8th century BC–238 BC), the Roman Republican and Imperial age (late 3rd century BC–first half of the 4th century AD), and finally the late Roman and early medieval age (up to the 7th-8th century AD).

