One of the earliest conflicts between the Persians and Greeks was the Ionian Revolt, which was instigated by some Greek regions against the Persian administration. The Greek cities were expressing their dissatisfaction towards their leaders who were appointed to the positions by Persia. The leaders (tyrants) enjoyed all the trappings of power and played an important role in the expansion of the Persian Empire in neighboring territories, to the displeasure of the Greek people.

Additionally, individual actions by some of the tyrants led to revolts. For instance, political intrigues between Histiaeus, former Chief of Miletus, and Aristagoras, his nephew and successor, led to the burning of Sardis, a Persian city. The Persians were forced to respond to the attacks and managed to contain the revolts.

The First Persian Invasion of Greece occurred in 490 BC. The invasion was carried out to punish the cities (Athens and Eretria) that supported the Ionian Revolt. Superior strategies helped the Athenians emerge victorious at the Battle of Marathon. However, despite the victory by the Athenians, the Persians had achieved most of their objectives after punishing Eretria and expanding their territory.

Territorial expansion was pursued by the Persians in the Second Persian Invasion. The second invasion was much larger than the first and was aimed at subjugating Greece. Despite early victories by the Persian forces, the Greek forces remained resolute and managed to change the course of the war in their favor. The Greeks managed to defeat the Persians and expelled them from their territories, including those that had been conquered earlier.

In summary, Persia's desire for political and territorial conquest was the main cause of the wars between Greece and Persia.

In 499 BCE, the Ionian Greek cities rebelled against the Persian empire. They sent ambassadors to Athens and other Greek cities asking for help. While Sparta refused to go to war against the enormous Persian Empire, Athens sent a small military force to join the rebels, who burned down the Persian provincial capital, Sardis. However, the Persian army eventually defeated the rebels in 494 BCE.

The Persian king Darius I was furious at Athens for helping the rebels. He perceived this as disloyalty on the part of Athenians because a few years earlier the Athenians had asked Persia for an alliance and agreed to offer Persians gifts of earth and water. For Persians, these gifts were a symbolic ceremony indicating that Athens had agreed to become a loyal vassal of the Persian king, but for the Athenians, who at that time were afraid that Sparta might attempt to destroy their democracy, the gifts meant an alliance between equals.

Darius decided to punish the Athenians for their disloyalty and in 490 BCE, he sent a small army commanded by Mardonius into Attica. The Athenians defeated this force at Marathon. In this way, they not only challenged the giant superpower but also demonstrated that Persian holdings in Asia Minor and, in particular, the Ionian cities would not remain safely under Persian control until Persians subjugated European Greece.

This was the conclusion to which Xerxes, the next king of Persia, came. Accordingly, in 484, he started preparing for a massive invasion of Greece, which he launched in 480 BCE. When the Greeks succeeded in defeating the enormous Persian Empire, they changed the course of history for Greece, Western Asia, Europe, and the world.

The Greeks and Persians went to war with each other because of the existence of Greek colonies in Asia Minor that had become part of the Persian Empire.  Greek cities in Asia Minor had become Persian subjects in the mid-sixth century BC.  Many of these cities were rebelling against the Persians because of their dislike of the Persian form of government.  Persia was an empire that did not give its subjects the same kinds of freedoms that the Greek poleis typically did.  Some city-states from mainland Greece helped the cities in Asia Minor rebel.  This led to the Persian Wars.