Local political power in Greater Syria—which probably would have continued to contest for control of the region—is effectively shattered when Alexander the Great conquers the Persian Empire in 333, and the area comes into the strong cultural orbit of Western ideas and institutions.

Alexander's empire is divided at his death among five of his generals.

General Seleucus becomes heir to the lands formerly under Persian control, which includes Greater Syria.

The Seleucids will rule for three centuries and found a kingdom later referred to as the Kingdom of Syria.

Seleucus names many cities after his mother, Laodicea; the greatest becomes Latakia, a major Syrian port.

An earthquake devastates the Syrian port town of Latakia in 494.

An earthquake devastates the city of Latakia (modern Syria) in 555.

An imperial fleet of ten ships is sent in 1099 to assist the Crusaders in capturing Laodicea and other coastal towns as far as Tripoli.

Meanwhile, Godfrey, along with Robert of Flanders, who had also refused vassalage to Raymond, joins together with the remaining Crusaders at Latakia and marches south in February.

Bohemond marches out with them but quickly returns to Antioch.

At this time, Tancred leaves Raymond's service and joins with Godfrey, due to some unknown quarrel.

Another separate force, though linked to Godfrey's, is led by Gaston IV of Béarn.

Tancred expands the frontiers of the principality to include the important port of Latakia, taken from the Empire in 1103.

Hulagu gives numerous gifts after the victory to Bohemond VI, including some of the conquered cities, including Latakia.

King Hugh III of Antioch had signed a treaty with Sultan Baibars concerning Latakia following the fall of the Principality of Antioch in 1268 to the Mamluks under Baibars.

Under the treaty, concluded on July 4, 1275, the town obtained its freedom from the Muslims in return for an annual tribute.

Remaining as a truncated Crusader enclave, Latakia had lost its prominence and was already declining as other ports, such as Tripoli and Alexandria, developed.

Baibars had been forced to surrender Latakia to Emir Sunkur of Damascus on July 24, 1281, but had regained control of the city after the fall of Sunkur.

In 1287, an earthquake devastates the town and causes widespread damage to the fortifications, destroying the Pigeon Tower, the Pier Tower and the lighthouse.

Taking advantage of this misfortune, Sultan Qalawun, who had already captured the great Hospitallers castle of Margat, immediately dispatches Emir Turuntay to attack the town.

On April 20, 1287, Latakia falls to Turuntay.