Within Greek mythology, this city is widely mentioned. Thebes is mentioned as the birthplace of Heracles, Dionysus, Niobe, Oedipus and Antigone. The local 'seven gates' and walls are said to have been built by the brothers Amphion and Zeus, with Amphion stacking blocks of stone by playing his lyre. The city castle of Cadmeia was, according to legend, built by the Phoenician Cadmus after he had slain a dragon that was ravaging the local landscape. One of Cadmus's sons was Oedipus, who passed the government to his sons Eteocles and Polyneices, with the understanding that the brothers would take turns ruling each year. Eteocles, however, violated this stipulation and did not relinquish his rule, which was the impetus for the campaign of the seven against Thebes.

During the period of the Greek city-states, Thebes was the largest and most important seat of Boeotia. It was also called "the city of seven gates".

Thebes belonged to the Boeotian confederation, where it was considered the capital of this group. During the Greco-Persian Wars, Thebes sided with Persia, with their major disagreements with Athens being the main motive. After the defeat of the Persians, however, Thebes lost its status as the capital of the Boeotian association, and the leaders of the Prophean party were executed. Sparta still had efforts to exclude Thebes from Delphic amphictyony, but this was prevented by Athens, which instead increased its influence over all of Boeotia. The influence of Thebes gradually declined.

In subsequent wars between Sparta and Athens, Thebes sided with Sparta. In return, Sparta again recognised Thebes as the capital of the Boeotian federation.

After the end of the Peloponnesian War, the Thebans abolished their alliance with Sparta because it brought them the same benefits as when Athens had power over them. This was followed by the alliance of Thebes with Athens, Argos and Corinth against Sparta, which was done with the generous support of Persian gold. The whole situation led to the Corinthian War, in which Thebes proved militarily successful, although it was ultimately defeated at the Battle of Corneille. The result was autonomy for all Greek municipalities, which meant the dissolution of the Boeotian confederation, and thus a much reduced influence of Thebes.

Subsequently, the city of Thebes was occupied by the Spartans, who were not driven out of the city until 379 BC, aided by the union of Thebes with Athens. Further disputes with Sparta followed, resulting in the Battle of Leukter in 371 BC, where Thebes was victorious and inflicted a crushing defeat on Sparta. This defeat broke the myth of Spartan invincibility and was also the first use of the so-called phalanx (withdrawal of the right wing and reinforcement of the rest of the formation).

The pressure on Sparta resulted in the disintegration of the Peloponnesian League and the diminished importance of Sparta. Conversely, the growing influence of Thebes resulted in the union of Athens and Sparta and then the Battle of Mantinea in 362 BC. Although this war was indecisive, the Theban king Epameinondas fell here. Thebes thus declined in importance to a mere regional city.

The last interesting Theban dispute stemmed from the growing influence of Philip II. Macedon. Against him, Thebes allied with Athens in an attempt to prevent his advance south. At the battle of Chaironeia, however, the Hellenes suffered a convincing defeat. This effectively ended their control of Greece itself.

Thebes was destroyed in 335 BC when a revolt broke out against Philip's son Alexander. The city was then rebuilt by Cassander in 315 BC, but it never regained its former importance.