Alexander, having appointed Antipater his deputy in Europe, now prepared to prosecute the war with Persia. He crossed the Hellespont in the spring of 334 B.C. with 30,000 foot and 5,000 horse, attacked the Persian satraps at the River Granicus, and gained a complete victory, overthrowing the son-in-law of their king Darius with his own lance. As a result of the battle, most of the cities of Asia Minor at once opened their gates to the conqueror.
Alexander restored democracy in all the Greek cities; and as he passed through Gordium, cut the Gordian-knot, which none should loose but the ruler of Asia. During a dangerous illness at Tarsus, brought on by bathing in the Cydnus, he received a letter insinuating that Philip, his physician, had been bribed by Darius to poison him. Alexander handed the letter to Philip, and at the same time swallowed the draught which the latter had prepared. As soon as he recovered, he advanced toward the defiles of Cilicia, in which Darius had stationed himself with an army of 600,000 men.
He arrived in November, 333 B.C., in the neighborhood of Issus, where, on the narrow plain between the mountains and the sea, the unwieldy masses of the Persians were thrown into confusion by the charge of the Macedonians, and fled in terror. On the left wing, 30,000 Greek mercenaries held out longer, but they, too, were at length compelled to yield. All the treasures as well as the family of Darius fell into the hands of the conqueror, who treated them with the greatest magnanimity. Overtures for peace, made by Darius on the basis of surrendering to Alexander all Asia west of the Euphrates, were rejected.
Alexander now turned toward Syria and Phoenicia. He occupied Damascus, where he found princely treasures, and secured to himself all the cities along the shores of the Mediterranean. Tyre, confident in its strong position, resisted him, but was conquered and destroyed, after seven months of incredible exertion (332 B.C.) Thence he marched victoriously through Palestine, where all the cities submitted to him except Gaza; it shared the same fate as Tyre. Egypt, weary of the Persian yoke, welcomed him as a deliverer; and in order to strengthen his dominion here, he restored all the old customs and religious institutions of the country, and founded Alexandria in the beginning of 331 B.C. Thence he marched through the Libyan Desert, in order to consult the oracle of Ammon, whose priest saluted him as a son of Zeus; and he returned with the conviction that he was indeed a god.