[3][4] Recent studies have revealed the site to have been inhabited and/or employed in an uninterrupted manner during a time span stretching back to the Bronze Age.

Stratonicea was a large Seleucid colony in Caria, settled by Macedonians and local Carians, in the mid-3rd century BCE.

[9] Seleucid kings conducted a considerable construction effort in the sacred ground of Lagina and transformed it into a foremost religious center of its time.

In 188 BCE, the Treaty of Apamea gave governance of Caria to Rhodes, an ally of the Roman Republic during the Roman–Seleucid war.

[5] Alongside the rest of Caria, Lagina and Stratonicea became part of the Roman province of Asia by the end of the 2nd century BCE.

The emperor Augustus himself donated a significant amount to help the site recover from damage after Lagina was attacked by Quintus Labienus, a rebel with Parthian support, in 40 BCE.

[5] Lagina was Christianised at an early date and was the seat of a bishop; no longer a residential see, it remains a titular see of the Roman Catholic Church.

Part of these rituals included a "Key-Carrying" ceremony in which a choir of young girls would walk from Lagina to Stratonicea to declare their devotion to the city.

The British archaeologist Charles Thomas Newton found over thirty inscriptions and nine decorated frieze blocks at the site in 1856.

The archaeological research conducted in Lagina is historically significant in that it was the first authorised excavation to have been done by a Turkish scientific team.

[5] In 1993, excavation and restoration work was resumed under the guidance of the Muğla Museum, by an international team advised by Professor Ahmet Tırpan.