It is supposed that until its destruction by the Persians in 494 BC, Didyma's sanctuary was administered by the family of the Branchidae, who claimed descent from an eponymous Branchos (Carian: 𐊷𐊠𐊥𐋄𐊠 parŋa), a youth beloved of Apollo. The priestess, seated above the sacred spring, gave utterances that were interpreted by the Branchidae. Both Herodotus and Pausanias dated the origins of the oracle at Didyma before the Ionian colonization of this coast. Clement of Alexandria quotes Leandrios saying that Cleochus, grandfather of the eponymous founder Miletus, was buried within the temple enclosure of Didyma.
Under the Persian king Darius, following the naval battle of Lade, the sanctuary was burned in 494 BC. The Persians carried away the bronze cult statue of Apollo to Ecbatana, traditionally attributed to Canachus of Sicyon at the end in the 6th century BC. It was then reported that the oracle spring ceased to flow and the archaic oracle was silenced. Although the sanctuaries of Delphi and Ephesus were swiftly rebuilt, Didyma remained a ruin until the time Alexander the Great conquered Miletus and freed it from the Persians in 334 BC. In between a complete break had been rent in the oracles' personnel and tradition, the Branchidae priests marched off to Persian sovereign territory. Callisthenes, a court historian of Alexander, reported that the spring began once more to flow as Alexander passed through Egypt in 331 BC.
After the liberation from the Persians the Milesians began to build a new temple for Apollo, which was the largest in the Hellenic world after the temple of Hera on the Isle of Samos and the temple of Artemis at Ephesus. Vitruvius recorded a tradition that the architects were Paeonius of Ephesus, whom Vitruvius credited with the rebuilding of the Temple of Artemis there, and Daphnis of Miletus. The dipteral temple of Apollo was surrounded by a double file of Ionic columns. From the pronaos lead two tunnels to the inner court. This was the location of the oracle spring, the sacred laurel tree and the naiskos - which was itself a small temple. It contained in its own small cella the bronze cult image of Apollo, brought back by Seleucus I Nicator from Persia about 300 BC.
In the Hellenistic period, beside Alexander, the kings Seleucus I and Seleucus II received oracles. So in the 3rd century BC the sanctuary of Apollo stood under the influence of the Seleucids, offering very rich donations to Apollo. Didyma suffered a serios setback in 277/76 BC, as Galatians looted it, coming from the Balkans to Asia Minor. Pliny reported the worship of Apollo Didymiae, Apollo of Didymus, in Central Asia, transported to Sogdiana
by a general of Seleucus I and Antiochus I whose inscribed altars there
were still to be seen by Pliny's correspondents. Corroborating
inscriptions on amphoras were found by I. R. Pichikyan at Dilbergin.Afterwards the kings of Bithynia made donations to the Didymaion in the 2nd century BC and the Ptolemaic kings of Egypt in the first half of 1st century BC.
The annual festival held in Didyma under the auspices of Miletus were called the Didymeia. They are first mentioned at the beginning 3rd century BC. A hundred years later they were made a Panhellenic (open to all Greeks) and a penteteric festival (they took place every four years). In the first half of the 1st century BC the Didymeia were banned because Miletus had supported Mithridates, in his war against the Romans. Furthermore, the sanctuary of Apollo was looted by pirates in 67 BC. After Pompey had reorganized the East of the Roman Empire, the Didymeia were permitted again in 63 BC. Some years later Gaius Iulius Caesar expanded the area under asylum in Didyma. Apparently the Roman emperor Caligula tried to complete the huge temple of Apollo. Emperor Trajan renewed the Sacred Way between Miletus and Didyma as inscriptions prove in 101 AD. His successor Hadrian visited Miletus and Didyma in 129 AD and acted as Prophet - the highest office in the sanctuary. Under Commodus the Didymeia were held as the Commodeia for the cult of the emperor.
In Hellenistic and Roman times the sanctuary of Apollo flourished again. Numerous oracles of Apollo were imparted, some of them are extant in Roman inscriptions. These included inquiries and responses, and literary testimony records Didyma's role as an oracle, with the "grim epilogue" of Apollo's supposed sanction of Diocletian's persecution of Christians, until the closing of the temples under Theodosius I. This was the end of the oracle. In Late Antiquity Didyma had been the seat of a bishop. Under Justinian I it was honoured with the title Iustinianopolis. In Byzantine times it changed the name to Hieronda deriving from the Greek name for sanctuary (hieron). This name was used for the village above the temple ruin until the early 20th century (Jeronda) and today the Turks continue to call it Yoran. About 1300 AD the Turks conquered this area of Ionia. Afterwards an earthquake in 1493 destroyed the temple of Apollo and the village was abandoned. About 300 years later the village was resettled by Greeks who used the broken ancient buildings as quarries.