伊苏斯战役（Battle of Issus），发生在前333年11月的安那托利亚西南方。年轻的亚历山大大帝率领马其顿军入侵至此，并击败数量比他多一倍的波斯大流士三世军，是亚历山大东征第二场重要战役。

在亚历山大于格拉尼库斯河战役成功击败波斯总督后，继续进军至小亚细亚西南部。而大流士三世率领从帝国各地招集的大军，进驻索契，但马其顿并没有出击迎战，大流士三世于是进军伊苏斯，从后方切断马其顿联军的补给线，迫使亚历山大回头与波斯军交战，战场在皮纳鲁斯河河口，位于伊苏斯村落的南方。

亚历山大担忧人数众多的波斯军队会从左方侧翼进行包抄，为了确保左翼安全，命令部队沿着海岸前进。又因波斯军先到达战场并占据有利的位置，使马其顿必须朝陡峭的河岸进攻。然而波斯兵力上的占优并没有为波斯带来胜利，波斯步兵素质的低劣断送了整场战事，让亚历山大成功突破波斯左翼数组。更重要的是，大流士三世在战争末段弃甲逃离战场，将士们顿时军心散漫，争相撤退，但在狭长的波斯阵地中难以撤退，被从后追到的马其顿军队屠杀，大流士三世的妻子及母亲及被俘虏。伊苏斯战役最终以大流士三世的逃阵告终，奠下波斯逐渐衰亡的道路。

The Battle of Issus occurred in southern Anatolia, in November 333 BC between the Hellenic League led by Alexander the Great and the Achaemenid Persia, led by Darius III, in the second great battle of Alexander's conquest of Asia. The invading Macedonian troops defeated Persia. After the Hellenic League soundly defeated the Persian satraps of Asia Minor (led by the Greek mercenary, Memnon of Rhodes) at the Battle of the Granicus, Darius took personal command of his army. He gathered reinforcements and led his men in a surprise march behind the Hellenic advance to cut their line of supply. This forced Alexander to countermarch, setting the stage for the battle near the mouth of the Pinarus River and the town of Issus.