In 499 BC, the Ionian city states under Persian rule rebelled against their Persian-supported tyrant rulers. Supported by troops sent from Athens and Eretria, they advanced as far as Sardis and burnt the city before being driven back by a Persian counterattack. The revolt continued until 494, when the rebelling Ionians were defeated. Darius did not forget that Athens had assisted the Ionian revolt, and in 490 he assembled an armada to retaliate. Though heavily outnumbered, the Athenians—supported by their Plataean allies—defeated the Persian hordes at the Battle of Marathon, and the Persian fleet turned tail.
Ten years later, a second invasion was launched by Darius' son Xerxes. The city-states of northern and central Greece submitted to the Persian forces without resistance, but a coalition of 31 Greek city states, including Athens and Sparta, determined to resist the Persian invaders. At the same time, Greek Sicily was invaded by a Carthaginian force. In 480 BC, the first major battle of the invasion was fought at Thermopylae, where a small rearguard of Greeks, led by three hundred Spartans, held a crucial pass guarding the heart of Greece for several days; at the same time Gelon, tyrant of Syracuse, defeated the Carthaginian invasion at the Battle of Himera.
The Persians were decisively defeated at sea by a primarily Athenian naval force at the Battle of Salamis, and on land in 479 BC at the Battle of Plataea. The alliance against Persia continued, initially led by the Spartan Pausanias but from 477 by Athens, and by 460 Persia had been driven out of the Aegean. During this long campaign, the Delian League gradually transformed from a defensive alliance of Greek states into an Athenian empire, as Athens' growing naval power intimidated the other league states. Athens ended its campaigns against Persia in 450, after a disastrous defeat in Egypt in 454, and the death of Cimon in action against the Persians on Cyprus in 450.
As the Athenian fight against the Persian empire waned, conflict grew between Athens and Sparta. Suspicious of the increasing Athenian power funded by the Delian League, Sparta offered aid to reluctant members of the League to rebel against Athenian domination. These tensions were exacerbated in 462 BC when Athens sent a force to aid Sparta in overcoming a helot revolt, but this aid was rejected by the Spartans. In the 450s, Athens took control of Boeotia, and won victories over Aegina and Corinth. However, Athens failed to win a decisive victory, and in 447 lost Boeotia again. Athens and Sparta signed the Thirty Years' Peace in the winter of 446/5, ending the conflict.
Despite the treaty, Athenian relations with Sparta declined again in the 430s, and in 431 BC the Peloponnesian War began. The first phase of the war saw a series of fruitless annual invasions of Attica by Sparta, while Athens successfully fought the Corinthian empire in northwest Greece and defended its own empire, despite a plague which killed the leading Athenian statesman Pericles. The war turned after Athenian victories led by Cleon at Pylos and Sphakteria, and Sparta sued for peace, but the Athenians rejected the proposal. The Athenian failure to regain control of Boeotia at Delium and Brasidas' successes in northern Greece in 424 improved Sparta's position after Sphakteria. After the deaths of Cleon and Brasidas, the strongest proponents of war on each side, a peace treaty was negoitiated in 421 by the Athenian general Nicias.
The peace did not last, however. In 418 BC allied forces of Athens and Argos were defeated by Sparta at Mantinea. In 415 Athens launched an ambitious naval expedition to dominate Sicily; the expedition ended in disaster at the harbour of Syracuse, with almost the entire army killed, and the ships destroyed. Soon after the Athenian defeat in Syracuse, Athens' Ionian allies began to rebel against the Delian league, while Persia began to once again involve itself in Greek affairs on the Spartan side. Initially the Athenian position continued relatively strong, with important victories at Cyzicus in 410 and Arginusae in 406. However, in 405 the Spartan Lysander defeated Athens in the Battle of Aegospotami, and began to blockade Athens' harbour; driven by hunger, Athens sued for peace, agreeing to surrender their fleet and join the Spartan-led Peloponnesian League. Following the Athenian surrender, Sparta installed an oligarchic regime, the Thirty Tyrants, in Athens, one of a number of Spartan-backed oligarchies which rose to power after the Peloponnesian war. Spartan predominance did not last: after only a year, the Thirty had been overthrown.
The first half of the fourth century saw the major Greek states attempt to dominate the mainland; none were successful, and their resulting weakness led to a power vacuum which would eventually be filled by Macedon under Philip II and then Alexander the Great. In the immediate aftermath of the Peloponnesian war, Sparta attempted to extend their own power, leading Argos, Athens, Corinth, and Thebes to join against them. Aiming to prevent any single Greek state gaining the dominance that would allow it to challenge Persia, the Persian king initially joined the alliance against Sparta, before imposing the Peace of Antalcidas ("King's Peace") which restored Persia's control over the Anatolian Greeks.
By 371 BC, Thebes was in the ascendancy, defeating Sparta at the Battle of Leuctra, killing the Spartan king Cleombrotus I, and invading Laconia. Further Theban successes against Sparta in 369 led to Messenia gaining independence; Sparta never recovered from the loss of Messenia's fertile land and the helot workforce it provided. The rising power of Thebes led Sparta and Athens to join forces; in 362 they were defeated by Thebes at the Battle of Mantinea. In the aftermath of Mantinea, none of the major Greek states were able to dominate. Though Thebes had won the battle, their general Epaminondas was killed, and they spent the following decades embroiled in wars with their neighbours; Athens, meanwhile, saw its second naval alliance, formed in 377, collapse in the mid-350s.
The power vacuum in Greece after the Battle of Mantinea was filled by Macedon, under Philip II. In 338 BC, he defeated a Greek alliance at the Battle of Chaeronea, and subsequently formed the League of Corinth. Philip planned to lead the League to invade Persia, but was murdered in 336. His son Alexander the Great was left to fulfil his father's ambitions. After campaigns against Macedon's western and northern enemies, and those Greek states that had broken from the League of Corinth following the death of Philip, Alexander began his campaign against Persia in 334. He conquered Persia, defeating Darius III at the Battle of Issus in 333, and after the Battle of Gaugamela in 331 proclaimed himself king of Asia. From 329 he led expeditions to Bactria and then India; further plans to invade Arabia and North Africa were halted by his death in 323.
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