The term originally referred to the "hollow" Beqaa Valley between the Lebanon and the Anti-Lebanon mountain ranges, but sometimes it was applied to a broader area of the region of Syria.

κοίλη (koílē) literally meaning 'hollow' in Ancient and Koine Greek, is thought to have come about via a folk-etymological reinterpretation referring to the "hollow" Beqaa Valley between Mount Lebanon and the Anti-Lebanon Mountains.

[11] According to Polybius, a former officer of the Ptolemaic Empire named Ptolemy Thrasea, having fought in the 217 BCE Battle of Raphia, defected to the Seleucid king Antiochus III the Great.

In 312 BC Seleucus I Nicator, defeated Demetrius, the son of Antigonus, in the Battle of Gaza which again allowed Ptolemy to occupy Coele-Syria.

The 171–168 BC conflicts over Coele-Syria, between Antiochus IV Epiphanes and Ptolemy VI Philometor, are discussed in Livy's history of Rome (in XLII.

Despite attempts of Seleucid rulers to regain territories, the conquests of Pompey in 64 BC were a decisive blow to them, and Syria became part of the Roman Republic.

Coele-Syria was allocated to Ptolemy's former ally Seleucus I Nicator, who—having been previously aided by Ptolemy—took no military action to gain control of the region.

The Geography of Strabo notes that Coele Syria Propria (Proper) is defined by the Libanus and Anti-libanus mountain ranges, running parallel to each other.

[29] When then [Moses] he received the supreme authority, with the good will of all his subjects, God himself being the regulator and approver of all his actions, he conducted his people as a colony into Phoenicia, and into the hollow Syria (Coele-syria), and Palestine, which was at that time called the land of the Canaanites, the borders of which country were three days' journey distant from Egypt.

[34] Syria had an uncertain border to the northeast that Pliny the Elder describes as including from west to east; Commagene, Sophene, and Adiabene.

It had a multitude of divisions with different names, the part adjacent to Arabia was previously known as Palestine (who's northernmost city was Caesarea, Plin.

[38][39]Antiochus made a friendship and league with Ptolemy, and gave him his daughter Cleopatra in marriage, and yielded up to him Cœle-Syria and Samaria and Judæa and Phœnicia by way of dowry.

[46][47] The governor of Syria retained the civil administration of the whole large province undiminished, and held for long alone in all Asia a command of the first rank.

[51] There is also the colony of Laodicea, in Coele Syria, to which also the divine Severus granted the Italian Law on account of its services in the Civil War.