The Roman Republic had been aggressively expanding in the southern Italian mainland for a century before the First Punic War. It had conquered peninsular Italy south of the River Arno by 272 BCE when the Greek cities of southern Italy (Magna Graecia) submitted at the conclusion of the Pyrrhic War. During this period Carthage, with its capital in what is now Tunisia, had come to dominate southern Spain, much of the coastal regions of North Africa, the Balearic Islands, Corsica, Sardinia, and the western half of Sicily, in a military and commercial empire. Beginning in 480 BCE Carthage had fought a series of inconclusive wars against the Greek city states of Sicily, led by Syracuse. By 264 BCE Carthage and Rome were the preeminent powers in the western Mediterranean. The two states had several times asserted their mutual friendship via formal alliances: in 509 BCE, 348 BCE and around 279 BCE. Relationships were good, with strong commercial links. During the Pyrrhic War of 280–275 BCE, against a king of Epirus who alternately fought Rome in Italy and Carthage on Sicily, Carthage provided materiel to the Romans and on at least one occasion used its navy to ferry a Roman force.

In 289 BCE a group of Italian mercenaries known as Mamertines, previously hired by Syracuse, occupied the city of Messana (modern Messina) on the north-eastern tip of Sicily. Hard-pressed by Syracuse, the Mamertines appealed to both Rome and Carthage for assistance in 265 BCE. The Carthaginians acted first, pressing Hiero II, king of Syracuse, into taking no further action and convincing the Mamertines to accept a Carthaginian garrison. According to Polybius, a considerable debate then took place in Rome as to whether to accept the Mamertines' appeal for assistance. As the Carthaginians had already garrisoned Messana acceptance could easily lead to war with Carthage. The Romans had not previously displayed any interest in Sicily and did not wish to come to the aid of soldiers who had unjustly stolen a city from its rightful owners. However, many of them saw strategic and monetary advantages in gaining a foothold in Sicily. The deadlocked Roman Senate, possibly at the instigation of Appius Claudius Caudex, put the matter before the popular assembly in 264 BCE. Caudex encouraged a vote for action and held out the prospect of plentiful booty; the popular assembly decided to accept the Mamertines' request. Caudex was appointed commander of a military expedition with orders to cross to Sicily and place a Roman garrison in Messana.