The wars between Rome and Carthage, the Punic Wars, were arguably the most critical Rome ever fought. Before the first, Rome was a purely Italian power and its forces had never operated outside peninsular Italy; by the end of the last, its armies had fought in Sicily, Africa, Albania, France, Spain, Greece, and Turkey, and it had acquired its first provinces in Sicily, Sardinia, Spain, and Africa and now dominated the Mediterranean world. After Hannibal's brief appearance before Rome in 211 (all dates are B.C. unless otherwise noted), it was to be over 600 years before a foreign enemy next appeared at Rome's gates.

The first war (264—241) was mainly fought in and around Sicily, apart from one or two Carthaginian raids on the Italian coast and a brief and disastrous Roman invasion of Africa in 256/5. It ended with the defeat of a Carthaginian fleet bringing supplies to the city's beleaguered army in Sicily. By the terms of the peace, Carthage was obliged to pay a huge indemnity and to withdraw its forces from Sicily and the islands between Sicily and Africa. Three years later, Rome used the opportunity of Carthage's involvement in a savage war with its mercenary army to increase the indemnity and seize Sardinia.