The first traces of human presence in Quartu are from the Prenuragic, Nuragic and Phoenician period, as attested by findings in Cepola, Geremeas, Is Mortorius and Separassiu localities.

In the 11th century AD Sardinia was divided into four Giudicati: Quartu, which included fourteen villas, belonged to the Giudicato of Cagliari.

During the Aragonese rule, Quartu suffered from famines, plague, malaria and continuous raids from Saracen pirates, following the general path of decay of the whole of Sardinia.

The most important are the churches of Sant'Elena Imperatrice (dating before 1589, but now in neoclassical style and recently proclaimed "Basilica"), Santa Maria Cepola (before 1089) and Sant'Agata.

In the 2012–13 season, it hosted Serie A club Cagliari Calcio, whose Stadio Sant'Elia was closed that year.