[citation needed] During the Second Punic War (218–201 BC), Rome recognised the strategic importance of the port of Puteoli and reinforced the defences and introduced a garrison to protect the town from Hannibal, who failed to capture it in 215.

[7] An alternative etymology of Puteoli derives from the Latin puteo (to stink), referring to the sulfuric fumes in the area, most notably from Solfatara.

It also was the main hub for goods exported from Campania, including blown glass, mosaics, wrought iron, and marble.

Many inscriptions show that a polyglot population established companies (stationes) for trade and transport and formed professional guilds for arts, crafts and religious associations for foreign cults; they included Greeks from the islands and the coast of Asia, Jews and later Christians.

[citation needed] The local volcanic sand, pozzolana (Latin: pulvis puteolanus, "dust of Puteoli") was the basis for Roman concrete, which reacted chemically with water, turning the sand/lime mix into a mortar strong enough to bind lumps of aggregate into a load-bearing unit.

[citation needed] There was a Nabataean community in the city that built a sanctuary at the port; it likely ended in the early second century CE when the site was filled with concrete.

[12] With the development of the port of Ostia begun by Claudius in 42 AD, completed by Nero in 54 and enlarged by Trajan between 100 and 106, the fortunes of Puteoli began to decline, although Antoninus Pius repaired the pier's storm damage in 139.

As a reward for their support in the fight against Vitellius, Vespasian (r. 69–79 AD) installed more veterans there, assigned the city a part of the Capuan territory and gave it the title Colonia Flavia which it retained.

Since 1946, the town has been the home of the Accademia Aeronautica, the Italian Air Force Academy, which was first situated on the island of Nisida, then from 1962 on a purpose-built hilltop campus overlooking the bay.