The three Punic Wars were to last for over a hundred years and during this struggle between the Carthaginians and the Romans, Sicily and its appendage, the Maltese islands, were to occupy central stage in the theatre of war for the control of the Mediterranean. By the end of the First Punic War, in 241 BC, the whole of Sicily had been ceded to the Romans but the Carthaginians were allowed to retain the Maltese Islands.

Peace did not last long, however, because in 218 BC a second war broke out and, learning from their past mistakes, the Romans were determined to capture the islands. Apparently the invasion did not present great difficulties and it has been suggested that the Phoenicians on the Island turned against their Carthaginian cousins and handed over the garrison to the invading Romans. The Maltese were treated more like allies than as a conquered people which lends some substance to the "collaboration" theory. The Maltese kept their Punic traditions and language and their gods. The two larger islands were renamed Melita and Gaulos and it has been tentatively suggested that the name Melita was not a Romanized version of the Phoenician Malet, but derived from mel (honey) for which the islands were then famous. With Carthage destroyed in the Third Punic War, and the Greeks overcome, the Mediterranean became a Roman Lake - the Mare Nostrum - the areas of conflict of imperial conquest now being the lands bordering this sea.

The Romans built the city of Melita, itself hearing the same name as that of the island, the city was built over an older, Punic settlement in what is now the Rabat/Mdina area in Malta, and also another town in Gozo under what is now Victoria (Rabat).