Lucullus now in turn proceeded to the aggressive. Triarius received the command of the fleet, with orders first of all to blockade the Hellespont and lie in wait for the Pontic ships returning from Crete and Spain; Cotta was charged with the siege of Heraclea; the difficult task of providing supplies was entrusted to the faithful and active princes of the Galatians and to Ariobarzanes king of Cappadocia; Lucullus himself advanced in the autumn of 681 into the favoured land of Pontus, which had long been untrodden by an enemy. Mithradates, now resolved to maintain the strictest defensive, retired without giving battle from Sinope to Amisus, and from Amisus to Cabira (afterwards Neocaesarea, now Niksar) on the Lycus, a tributary of the Iris; he contented himself with drawing the enemy after him farther and farther into the interior, and obstructing their supplies and communications.

Lucullus rapidly followed; Sinope was passed by; the Halys, the old boundary of the Roman dominion, was crossed and the considerable towns of Amisus, Eupatoria (on the Iris), and Themiscyra (on the Thermodon) were invested, till at length winter put an end to the onward march, though not to the investments of the towns. The soldiers of Lucullus murmured at the constant advance which did not allow them to reap the fruits of their exertions, and at the tedious and - amidst the severity of that season - burdensome blockades. But it was not the habit of Lucullus to listen to such complaints: in the spring of 682 he immediately advanced against Cabira, leaving behind two legions before Amisus under Lucius Murena. The king had made fresh attempts during the winter to induce the great-king of Armenia to take part in the struggle; they remained like the former ones fruitless, or led only to empty promises. Still less did the Parthians show any desire to interfere in the forlorn cause. Nevertheless a considerable army, chiefly raised by enlistments in Scythia, had again assembled under Diophantus and Taxiles at Cabira. The Roman army, which still numbered only three legions and was decidedly inferior to the Pontic in cavalry, found itself compelled to avoid as far as possible the plains, and arrived, not without toil and loss, by difficult bypaths in the vicinity of Cabira, At this town the two armies lay for a considerable period confronting each other.

The chief struggle was for supplies, which were on both sides scarce: for this purpose Mithradates formed the flower of his cavalry and a division of select infantry under Diophantus and Taxiles into a flying corps, which was intended to scour the country between the Lycus and the Halys and to seize the Roman convoys of provisions coming from Cappadocia. But the lieutenant of Lucullus, Marcus Fabius Hadrianus, who escorted such a train, not only completely defeated the band which lay in wait for him in the defile where it expected to surprise him, but after being reinforced from the camp defeated also the army of Diophantus and Taxiles itself, so that it totally broke up. It was an irreparable loss for the king, when his cavalry, on which alone he relied, was thus overthrown.

As soon as he received through the first fugitives that arrived at Cabira from the field of battle - significantly enough, the beaten generals themselves - the fatal news, earlier even than Lucullus got tidings of the victory, he resolved on an immediate farther retreat. But the resolution taken by the king spread with the rapidity of lightning among those immediately around him; and, when the soldiers saw the confidants of the king packing in all haste, they too were seized with a panic. No one was willing to be the hindmost in decamping; all, high and low, ran pell-mell like startled deer; no authority, not even that of the king, was longer heeded; and the king himself was carried away amidst the wild tumult. Lucullus, perceiving the confusion, made his attack, and the Pontic troops allowed themselves to be massacred almost without offering resistance. Had the legions been able to maintain discipline and to restrain their eagerness for spoil, hardly a man would have escaped them, and the king himself would doubtless have been taken. With difficulty Mithradates escaped along with a few attendants through the mountains to Comana (not far from Tocat and the source of the Iris); from which, however, a Roman corps under Marcus Pompeius soon scared him off and pursued him, till, attended by not more than 2000 cavalry, he crossed the frontier of his kingdom at Talaura in Lesser Armenia. In the empire of the great-king he found a refuge, but nothing more (end of 682). Tigranes, it is true, ordered royal honours to be shown to his fugitive father-in-law; but he did not even invite him to his court, and detained him in the remote border-province to which he had come in a sort of decorous captivity.

The Roman troops overran all Pontus and Lesser Armenia, and as far as Trapezus the flat country submitted without resistance to the conqueror. The commanders of the royal treasure-houses also surrendered after more or less delay, and delivered up their stores of money. The king ordered that the women of the royal harem - his sisters, his numerous wives and concubines - as it was not possible to secure their flight, should all be put to death by one of his eunuchs at Pharnacea (Kerasunt). The towns alone offered obstinate resistance. It is true that the few in the interior - Cabira, Amasia, Eupatoria - were soon in the power of the Romans; but the larger maritime towns, Amisus and Sinope in Pontus, Amastris in Paphlagonia, Tius and the Pontic Heraclea in Bithynia, defended themselves with desperation, partly animated by attachment to the king and to their free Hellenic constitution which he had protected, partly overawed by the bands of corsairs whom the king had called to his aid. Sinope and Heraclea even sent forth vessels against the Romans; and the squadron of Sinope seized a Roman flotilla which was bringing corn from the Tauric peninsula for the army of Lucullus. Heraclea did not succumb till after a two years' siege, when the Roman fleet had cut off the city from intercourse with the Greek towns on the Tauric peninsula and treason had broken out in the ranks of the garrison. When Amisus was reduced to extremities, the garrison set fire to the town, and under cover of the flames took to their ships. In Sinope, where the daring pirate-captain Seleucus and the royal eunuch Bacchides conducted the defence, the garrison plundered the houses before it withdrew, and set on fire the ships which it could not take along with it; it is said that, although the greater portion of the defenders were enabled to embark, 8000 corsairs were there put to death by Lucullus. These sieges of towns lasted for two whole years and more after the battle of Cabira (682-684); Lucullus prosecuted them in great part by means of his lieutenants, while he himself regulated the affairs of the province of Asia, which demanded and obtained a thorough reform.

Remarkable, in an historical point of view, as was that obstinate resistance of the Pontic mercantile towns to the victorious Romans, it was of little immediate use; the cause of Mithradates was none the less lost. The great-king had evidently, for the present at least, no intention at all of restoring him to his kingdom. The Roman emigrants in Asia had lost their best men by the destruction of the Aegean fleet; of the survivors not a few, such as the active leaders Lucius Magius and Lucius Fannius, had made their peace with Lucullus; and with the death of Sertorius, who perished in the year of the battle of Cabira, the last hope of the emigrants vanished.