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The movie begins with Ptolemy I Soter narrating the key events of Alexander's life and events revolving around his invasion of the Achaemenid Empire (Persian Empire). He Alexander was declared a god in Egypt and then found fought the pivotal Battle of Gaugamela, where the Persian army was defeated and later fell, although Alexander failed to kill or capture the Persian king, forcing him to march further east. The story then goes back in time to show the strained relationship between Alexander's mother (Olympias) and Philip II. Alexander takes solace in wrestling, horse riding, and becomes tutored by Aristotle.

After Alexander is declared king and unites the Greeksafter his father's death, his campaign against the Persians commences. One After his victory in Gaugamela, one key focus was on Alexander entering Babylon, one of the great cities of the Achaemenid (Persian) Empire. Alexander is depicted as being in awe of the great city and showed more interest in uniting the Persian world with the Greek world, where he is the great king of this new united world. While his soldiers delight in his great victory, Alexander is shown as thinking more about the futureand freeing those who were enslaved at the Persian court. He gives permission for royal individuals , including Darius' daughter, to remain and be treated with respect. Meanwhile, while Alexander is staying in Babylon, his mother makes him aware of conspiracies against him but berates him for being too generous with his enemies. Alexander is shown as conflicted about his destiny. Hephaistion, one of Alexander's generals, is shown as his close companion, confidant, and lover.

Alexander then pushed on into Central Asia and India, where Alexander finally marries , choosing Roxana, a Persian-Bactrian princess that was also intended to help unify the worlds that Alexander wanted to conquer. The Greek generals and soldiers are not completely convinced in this marriage, as the Greeks saw the newly conquered as barbarians. Alexander, though, seems to be happy with her, despite Hephaistion's possible jealousy. Later, one of Alexander's close strategists, Parmenion, is assassinated as he was accused of treason against Alexander. LaterThen, Cleitus, an officer of serving Alexander, who was to be governor of Bactria, got involved in a drunken dispute with Alexander, where Cleitus insulted Alexander, leading to Alexander killing Cleitus. This event and assassination of Parmenion showed the increased strain Alexander and his men were coming under as they had campaigned for so long away from Macedonia. Alexander offers generous rewards and pensions to his soldiers to keep their loyaltyas he continues east.

Alexander then pushes his men where they fight the Battle of Hydaspesin Punjab, India. Alexander is shown as being gravely injured and the battle being particularly bloody, although the battle was won by Alexander and his troops. His army was, at this point, was exhausted and many men perished as they marched back to Babylon. Back in Babylon, Alexander was shown as trying to forge a united Greek and eastern state that combined Persian and other eastern populations. His lover Hephaistion dies from Typhus and a few months later Alexander joins him in death. With Alexander's death, his generals divide his kingdom. Ptolemy is shown as creating a biography about Alexander, where the movie suggests the generals poisoned Alexander and sickness did not kill him, as the generals feared Alexander may have wanted to launch new campaigns to the dismay of his soldiers.