The sanctuary of Dodona, the religious centre for northwestern Greece, closely related to the cult of Zeus, father of the gods, lies in the narrow valley east of Tomaros. Dodona was also known for its famous oracle, traditionally considered as the most ancient one in Greece and referred to by Homer in his epics. Herodotus (2.52) relates a myth regarding the establishment of the sanctuary, narrated to him by the sanctuary's priests on his visit to Dodona: two black pigeons, the peleiades, flew from Thebes in Egypt; one of them landed in Libya, where the temple of Ammon Zeus was subsequently erected; the other one reached Dodona, where it sat on an oak tree, Zeus's sacred tree, and spoke in a human voice, indicating the spot where the god's oracle was to be built. By observing the rustling of the leaves on the sacred oak tree and the flight of the birds nesting in it the priests interpreted the god's will. The oracles were based on the murmuring of the waters from the ancient spring and on the sound produced by bronze cauldrons standing on tripods around the sacred tree. According to ancient sources, the priests of the oracle were originally only men, but priestesses, the so-called Peleiades, appear in later times. The priests and priestesses were famous for walking barefoot and for sleeping on the ground so as to be in immediate contact with the earth.

Archaeological evidence suggests that the area was occupied since the Bronze Age. The earliest cult was probably dedicated to the Earth goddess or to another female deity related to fertility. The cult of Zeus, brought to Dodona by the Selloi, a tribe from Thesprotia, soon became the main cult. Zeus Naios was worshipped together with Dioni, his wife, according to local tradition. Later, the cult of Aphrodite, their daughter, was also introduced, together with that of Themis. Dioni and Themis were worshipped as 'naian gods' - that is, gods who shared the same house (synoikoi) and temple (synnaioi) as Zeus.

Originally the sanctuary was outdoors, and various ceremonies were performed around the sacred tree (sacred oak or fagus), in which the divine couple, Zeus and Dioni, resided. Offerings, such as bronze tripods, statuettes, jewellery, and weapons, from southern Greece reached the sanctuary as early as the eighth century BC, indicating that settlers from Greek cities were colonizing the shores of Epirus. Dodona, however, did not witness the intense building activity of other famous sanctuaries, such as Delphi, Olympia, and Delos, during this period, probably because it was isolated from the rest of Greece and far from all major commercial routes. The sanctuary remained outdoors, and the sacred area of the tree was defined by a kind of enclosure formed by bronze cauldrons.

The first signs of building activity date to the early fourth century BC, when the first small temple of Zeus and three Ionic stoas were erected. The enclosure of the Dodona acropolis, further north, dates to the same period. The sanctuary thrived in the third century BC under King Pyrrhus (297-272 BC), who gave it its monumental character. The rest of the temples and the sanctuary's most impressive buildings, including the theatre, the bouleuterion, the prytaneum, and the stadium, which hosted the Naian Games held in honour of Zeus, were all erected during this period. The sanctuary was destroyed by the Aetolians in 219 BC, but was soon reconstructed and functioned again until 167 BC, when it was destroyed by the Romans. It suffered again in 88 BC under Mithridates VI Eupator, King of Pontus, and his Thracian warriors. The sanctuary was reestablished in the Roman period, although with a different character, and its theatre was converted into an arena, which Emperor Hadrian visited around 132 AD. The oracle and festivities in honour of Zeus continued to attract worshipers until the fourth century BC. Christianity, however, gradually replaced the old religion, Christian basilicas were erected inside the sacred precinct, and the sacred oak was cut down.

Excavations by K. Karapanos in 1875 identified the sanctuary and yielded a large number of finds. Another short-termed excavation began after 1913 by the Archaeological Society in Athens under G. Sotiriadis, but was interrupted by the political events of 1921. D. Evangelidis continued the investigations from 1929 until 1932. Systematic excavations began in the 1950s under Evangelidis and S. Dakaris, and continued under Dakaris alone after Evangelidis's death in 1959. Since 1981 excavations have been carried out under the auspices of the Archaeological Society of Athens and are co-funded by the University of Ioannina. The systematic consolidation and restoration of the theatre, stadium, and other monuments, according to a study by the architect V. Charisis, began after 1961 with funds provided by the Archaeological Society and the Programme for Public Investments. The theatre, most of which was restored by 1975 (apart from the third landing and a few other parts), now hosts theatrical performances.