Final answer:
Alexander the Great defeated Darius III at the Battle of Issus in 333 BCE.
Step-by-step explanation:
Alexander the Great defeated Darius III at the Battle of Issus in 333 BCE. This battle took place in present-day Turkey and was a significant victory for the Macedonians. Alexander's forces, commanded by himself, outmaneuvered and defeated Darius' Persian army, marking a major turning point in the war between the two empires.