In the meanwhile Carthage, which hitherto had only supported the Syracusans with her fleets, on receiving news of their renewed rising in arms against the Romans had despatched a strong land army under Himilco to Sicily, which landed without interruption at Heraclea Minoa and immediately occupied the important town of Agrigentum. To effect a junction with Himilco, the bold and able Hippocrates marched forth from Syracuse with an army: the position of Marcellus between the garrison of Syracuse and the two hostile armies began to be critical. With the help of some reinforcements, however, which arrived from Italy, he maintained his position in the island and continued the blockade of Syracuse. On the other hand, the greater portion of the small inland towns were driven to the armies of the Carthaginians not so much by the armies of the enemy, as by the fearful severity of the Roman proceedings in the island, more especially the slaughter of the citizens of Enna, suspected of a design to revolt, by the Roman garrison which was stationed there. In 542 the besiegers of Syracuse during a festival in the city succeeded in scaling a portion of the extensive outer walls that had been deserted by the guard, and in penetrating into the suburbs which stretched from the "island" and the city proper on the shore (Achradina) towards the interior. The fortress of Euryalus, which, situated at the extreme western end of the suburbs, protected these and the principal road leading from the interior to Syracuse, was thus cut off and fell not long afterwards.
When the siege of the city thus began to assume a turn favourable to the Romans, the two armies under Himilco and Hippocrates advanced to its relief, and attempted a simultaneous attack on the Roman positions, combined with an attempt at landing on the part of the Carthaginian fleet and a sally of the Syracusan garrison; but the attack was repulsed on all sides, and the two relieving armies were obliged to content themselves with encamping before the city, in the low marshy grounds along the Anapus, which in the height of summer and autumn engender pestilences fatal to those that tarry in them. These pestilences had often saved the city, oftener even than the valour of its citizens; in the times of the first Dionysius, two Phoenician armies in the act of besieging the city had been in this way destroyed under its very walls. Now fate turned the special defence of the city into the means of its destruction; while the army of Marcellus quartered in the suburbs suffered but little, fevers desolated the Phoenician and Syracusan bivouacs. Hippocrates died; Himilco and most of the Africans died also; the survivors of the two armies, mostly native Siceli, dispersed into the neighbouring cities. The Carthaginians made a further attempt to save the city from the sea side; but the admiral Bomilcar withdrew, when the Roman fleet offered him battle. Epicydes himself, who commanded in the city, now abandoned it as lost, and made his escape to Agrigentum. Syracuse would gladly have surrendered to the Romans; negotiations had already begun. But for the second time they were thwarted by the deserters: in another mutiny of the soldiers the chief magistrates and a number of respectable citizens were slain, and the government and the defence of the city were entrusted by the foreign troops to their captains. Marcellus now entered into a negotiation with one of these, which gave into his hands one of the two portions of the city that were still free, the "island"; upon which the citizens voluntarily opened to him the gates of Achradina also (in the autumn of 542). If mercy was to be shown in any case, it might, even according to the far from laudable principles of Roman public law as to the treatment of perfidious communities, have been extended to this city, which manifestly had not been at liberty to act for itself, and which had repeatedly made the most earnest attempts to get rid of the tyranny of the foreign soldiers. Nevertheless, not only did Marcellus stain his military honour by permitting a general pillage of the wealthy mercantile city, in the course of which Archimedes and many other citizens were put to death, but the Roman senate lent a deaf ear to the complaints which the Syracusans afterwards presented regarding the celebrated general, and neither returned to individuals their pillaged property nor restored to the city its freedom. Syracuse and the towns that had been previously dependent on it were classed among the communities tributary to Rome - Tauromenium and Neetum alone obtained the same privileges as Messana, while the territory of Leontini became Roman domain and its former proprietors Roman lessees - and no Syracusan citizen was henceforth allowed to reside in the "island", the portion of the city that commanded the harbour.
Sicily thus appeared lost to the Carthaginians; but the genius of Hannibal exercised even from a distance its influence there. He despatched to the Carthaginian army, which remained at. Agrigentum in perplexity and inaction under Hanno and Epicydes, a Libyan cavalry officer Muttines, who took the command of the Numidian cavalry, and with his flying squadrons, fanning into an open flame the bitter hatred which the despotic rule of the Romans had excited over all the island, commenced a guerilla warfare on the most extensive scale and with the happiest results; so that he even, when the Carthaginian and Roman armies met on the river Himera, sustained some conflicts with Marcellus himself successfully. The relations, however, which prevailed between Hannibal and the Carthaginian council, were here repeated on a small scale. The general appointed by the council pursued with jealous envy the officer sent by Hannibal, and insisted upon giving battle to the proconsul without Muttines and the Numidians. The wish of Hanno was carried out, and he was completely beaten. Muttines was not induced to deviate from his course; he maintained himself in the interior of the country, occupied several small towns, and was enabled by the not inconsiderable reinforcements which joined him from Carthage gradually to extend his operations. His successes were so brilliant, that at length the commander-in-chief, who could not otherwise prevent the cavalry officer from eclipsing him, deprived him summarily of the command of the light cavalry, and entrusted it to his own son. The Numidian, who had now for two years preserved the island for his Phoenician masters, had the measure of his patience exhausted by this treatment. He and his horsemen who refused to follow the younger Hanno entered into negotiations with the Roman general Marcus Valerius Laevinus and delivered to him Agrigentum. Hanno escaped in a boat, and went to Carthage to report to his superiors the disgraceful high treason of Hannibal's officer; the Phoenician garrison in the town was put to death by the Romans, and the citizens were sold into slavery (544). To secure the island from such surprises as the landing of 540, the city received a new body of inhabitants selected from Sicilians well disposed towards Rome; the old glorious Akragas was no more. After the whole of Sicily was thus subdued, the Romans exerted themselves to restore some sort of tranquillity and order to the distracted island. The pack of banditti that haunted the interior were driven together en masse and conveyed to Italy, that from their head-quarters at Rhegium they might burn and destroy in the territories of Hannibal's allies. The government did its utmost to promote the restoration of agriculture which had been totally neglected in the island. The Carthaginian council more than once talked of sending a fleet to Sicily and renewing the war there; but the project went no further.