The town was founded in the 4th century BC by the Volsci, who successfully defended it against Samnite invasions, before the Roman conquest. Ancient Aquinum was a municipium in the time of Cicero, and made a colony by the Triumviri. It was crossed by the Via Latina.

Aquinum is thought to be the birthplace of the poet Juvenal, and Emperor Pescennius Niger was also born there.

The earliest, recorded Catholic Bishop of Aquino was Bishop Giovino in 593 AD.

The patron saint of Aquino is St. Constantius of Aquino (San Costanzo).St. Thomas Aquinas, OP, or "Thomas of Aquino", was born in 1225 in the castle of Roccasecca, 8 kilometres (5 mi) north of Aquino, to a collateral branch of the family of the Counts of Aquino, whose primary seat was Aquino.

One of the gates through which the Via Latina passed, now called Porta San Lorenzo, is still well preserved, and there are remains within the walls (portions of which, built of large blocks of limestone, still remain) of two (so called) temples, a basilica and an amphitheatre.

Outside, on the south is a well-preserved 1st century BC triumphal arch with composite capitals, known as Arco di Marcantonio, and close to it the basilica of Santa Maria Libera, a 9th-century building in the Romanesque style erected over the remains of an ancient temple of Hercules Liberator, now roofless. Several Roman inscriptions are built into it, and many others that have been found indicate the ancient importance of the place, which, though it does not appear in early history, is vouched for by Cicero and Strabo.

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