The First Punic War, 264–241 B.C., grew immediately out of a quarrel between the Sicilian cities of Messana (now Messina) and Syracuse. One faction of the Messanians called on Carthage for help and another faction called on Rome. The Strait of Messana, which separates the Italian Peninsula from Sicily, was of extreme strategic importance, and both powers responded. The Punic army arrived in Sicily first, arranged a peace between Messana and Syracuse, and established a garrison. Upon its arrival, the Roman army ejected the Carthaginians from the garrison, and thus the war began.

Roman legions occupied E Sicily, and the newly created Roman fleet, after victories at Mylae (260) and off Cape Ecnomus (256), landed a force in Africa. This excursion was a failure, and its commander, Regulus, was captured (255) by the Greek mercenary general Xanthippus. In Sicily the Romans took Palermo (254) but were effectively blocked farther west by the brilliant guerrilla warfare of Hamilcar Barca, and they failed to take Lilybaeum, the chief Punic base. The Romans equipped a new fleet that destroyed (241) the Punic fleet off the Aegates (now Aegadian Isles), and Carthage sued for peace. The terms were the payment of an indemnity and the cession of Punic Sicily to Rome. The chief events of the next 20 years were the Roman entry into Sardinia and Corsica—a gross breach of treaty—and the conquests in Spain by Hamilcar.

When Hamilcar Barca's son Hannibal took (219) the Spanish city of Saguntum (present-day Sagunto), a Roman ally, Rome declared war. This Second Punic, or Hannibalic, War, 218–201 B.C., was one of the titanic struggles of history. Rome owed its success to various factors: its stubborn will and splendid military organization; its superior economic resources; its generals, Fabius and, above all, Scipio; the failure of supply from Carthage to Hannibal's Italian army; and the mountainous character of central Italy, which rendered the Punic superiority in cavalry nearly useless. For the course of the war, see Hannibal and Scipio Africanus Major. At the war's close, Carthage surrendered to Rome its Spanish province and its war fleet.

The Third Punic War, 149–146 B.C., originated, like the others, in a deliberate Roman aggression, the result of agitation by Cato the Elder for the destruction of Carthage. Charging Carthage with a technical breach of treaty in resisting the encroachment of the Numidian king Masinissa (a Roman ally), Rome declared war and blockaded the city. Carthage never surrendered. The younger Scipio (Scipio Africanus Minor) conquered it, house by house, and sold the surviving inhabitants into slavery. The city was razed and its site plowed up.