Alexander III inherited both his empire and his plans from his father, Philip II. This man had first restored the regional primacy of Macedon, then conquered Thessaly and Thrace up to the Danube, and then subdued the city-states of Greece. He did not put these under the charge of governors or pro-Macedonian oligarchies, but rather founded the League of Corinth, which required the Greek states to contribute troops and money to a Macedonian-led campaign of conquest against Persia.

Plans to wage war on Persia were generations old by this time. Many Greeks believed that the exploits of the Ten Thousand were proof that Persia could be easily defeated on land. Agesilaos' campaigns in Asia Minor in 396-395 BC were generally seen as a success, reinforcing the notion that the Greeks would find it easy to take lands away from the Great King. However, in practice, the Persians played a shrewd divide-and-rule game with the Greek city-states that left them firmly in control of Asia Minor after 394 BC. Increasing frustration with the influence of the Persians on Greek affairs (as expressed in the King's Peaces of 387/6 BC, 375 BC, 371 BC, 367 BC, 365/4 BC and 361 BC) fuelled the rise of the movement of panhellenism, whose aim was to unite the Greeks against Persia. In 380 BC, the Athenian author Isokrates suggested that Athens should lead this righteous campaign of conquest, but by 346 BC he had realised that Philip was the most powerful man in Greece, and that he was the only likely candidate to lead a collective Greek effort. We don't know if the speech Isokrates wrote to Philip at this time persuaded him, but the similarity between his suggestions and Philip's eventual plans are striking.

This was the situation when Alexander became king. Much of the Balkans was already under Macedonian control, and there didn't seem to be much further north that was worth taking. Meanwhile there was a strong cultural and political incentive to go east, which coincided with the fact that Persia was very large, very rich, and thought to be very weak.

Now, Isokrates actually suggested that the Greeks should only take Asia Minor, or if that was too much, just the cities on the western coast of modern Turkey; he never would have imagined that it was possible to topple the entire empire. However, Alexander seems to have been a uniquely relentless individual, driving ever further eastwards where any other Greek leader would have stopped and consolidated his gains. It would perhaps have been impossible to persuade such a character to turn his advance in another direction before it was complete.