The Battle of Issus,(333BC) Alexander the Great of Macedonia defeated Darius III of Persia. This battle is occasionally called the First Battle of Issus, but is more generally known simply as the Battle of Issus, owing to the importance of Alexander's victory over the First Persian Empire and its impact on subsequent history of the region, including all the successor polities.It was the first time the Persian army had been defeated with the King (Darius III at the time) present. It marked the beginning of the end of Persian power
Battle of Issus (194), or Second Battle of Issus — between the forces of Emperor Septimus Severus and his rival, Pescennius Niger.
Battle of Issus (622), or Third Battle of Issus — between the Byzantine Empire and the Sassanid Persian Empire. That the Byzantines would triumph in this battle was allegedly prophesied by Mohammed.