The Macedonian conqueror turns twenty-six at Thapsacus on the Euphrates in July 331.

Instead of taking the direct route down the river to Babylon, …

…Alexander crosses northern Mesopotamia toward the Tigris, and Darius, learning of this move from an advance force sent under Mazaeus to the Euphrates crossing, marches up the Tigris to oppose him.

In an attempt to stop Alexander's incursion into the Persian empire, Darius prepares a battleground on the Plain of Gaugamela, between Nineveh and Arbela (present-day Irbil in northern Iraq), and posts his two hundred and fifty thousand troops to await Alexander's advance.

Darius has the terrain of the prospective battlefield smoothed level so that his many chariots can operate with maximum effectiveness against the Macedonians.

Alexander's well-trained but greatly outnumbered army faces Darius' massive battle line on October 1, 331 BCE, and organizes for attack, charging the left of the Persians' line with archers, javelin throwers, and cavalry, while defending against Darius' outflanking cavalry with reserve flank guards.

During the combat, so much of Darius' cavalry on his left flank are drawn into the battle that they leave exposed the Persian infantry in the center of the battle line.

Alexander and his personal cavalry immediately wheel half left and penetrate this gap, then wheel again to attack the Persians' flank and rear.

At this, Darius turns his chariot and flees, as at Issus.

Although his subordinates fight on, panic spreads through his entire army, which soon begins a headlong retreat while being cut down by the pursuing Greeks.

The Macedonians suffer fewer than five hundred casualties; the Persians lose an estimated forty thousand to ninety thousand men.

Alexander pursues the defeated Persian forces for thirty-five miles to …

…Arbela, but …

…Darius escapes with his Bactrian cavalry and Greek mercenaries into Media.

Alexander may have had a great advantage in linothrax, a Kevlar-like body armor made by laminating together layers of linen.

Widely mentioned in ancient records, the main visual evidence for Alexander wearing linothrax is the famous Alexander mosaic from Pompeii, which depicts the Macedonian conquerer wearing this sort of armor.

Plutarch, in his Life of Alexander, states that Alexander wore “a breastplate of folded [or doubled] linen” at the Battle of Gaugamela.

Linothrax apparently used the flexibility of the fabric to disperse the force of the incoming arrow or other projectiles, providing ample protection under extreme conditions.

A few years after Gaugamela, when Alexander is in India and receives twenty-five thousand new suits of armor for his forces, he is described as ordering the old, worn-out suits to be burned—an indication that said armor is not made of metal but of fabric.

Alexander now occupies Babylon, city and province; the cultural influence of this rich provincial capital extends far beyond Mesopotamia.

Mazaeus, who surrenders it, is reappointed as satrap in conjunction with Macedonians to supervise the garrison and the finances, and quite exceptionally is granted the right to coin.

As in Egypt, the local priesthood is encouraged.

Susa, the effective if not official Achaemenid capital, also surrenders, releasing huge treasures amounting to fifty thousand gold talents; here Alexander establishes Darius' family in comfort.

Like Mazaeus, the Persian Abulites is confirmed in the Susa satrapy.

Alexander employs Egyptian governors to organize the administration during the winter, and keeps the army under a separate Macedonian command.

He reportedly sends an expedition from Alexandria in 331 to discover the causes of the flooding of the Nile.

Leaving his viceroy, Cleomenes, to continue the creation of Alexandria, …

…Alexander returns in spring 331 BCE to Tyre, appoints a Macedonian satrap for Syria, and prepares to advance into Mesopotamia, his conquest of Egypt having completed his control of the eastern Mediterranean coast.

Alexander's mother Olympias has quarreled repeatedly with the regent Antipater, whose main task is to hold Macedon’s northern frontiers against hostile tribes and to keep order among the Greek states.

He rules Greece by cooperating with the League of Corinth but is unpopular because he supports oligarchic governments.

Olympias in about 331 eventually retires again to Epirus.

Agis III of Sparta, profiting from the Macedonian king's absence from Greece, leads some of the Greek cities in a revolt.

With Persian money and eight thousand Greek mercenaries, he holds Crete against Macedonian forces.

He routs a force in the Peloponnesus under the Macedonian general Coragus.

Although Athens stays neutral, Agis is joined by Elis, Achaea (except Pellene) and Arcadia, with the exception of Megalopolis, the staunchly anti-Spartan capital of Arcadia, which the Spartan forces in 331 besiege.