The site lies on the edge of the modern town of Qalaat al-Madiq, about 55 km (34 mi) to the northwest of Hama, Syria, overlooking the Ghab valley.

After the conquest of the region by Alexander the Great and the subsequent wars between his generals, and according to the new interpretation of a new historical and iconographic source for Hellenistic history, a mosaic of Apamea discovered in 2011, proposed by Olszewski and Saad,[2] the foundation of Pella, the Macedonian military camp (katoikia) took place in the fall 320 BC, just after the Treaty of Triparadeisos (320 BC) at the initiative of Antipater, and Cassander's inspiration.

In view of this interpretation, the authors disagree with the earlier hypothesises attributing the foundation of Pella to Alexander the Great or to Antigonus I Monophthalmus.

[3] The site was enclosed in a loop of the Orontes which, with the lake and marshes, gave it a peninsular form whence its other name of Cherronêsos.

[6] In 64 BC, Pompey marched south from his winter quarters probably at or near Antioch and razed the fortress of Apamea when the city was annexed to the Roman Republic.

[7] In the revolt of Syria under Quintus Caecilius Bassus, it held out against Julius Caesar for three years till the arrival of Cassius in 46 BC.

[8] On the outbreak of the Jewish War, the inhabitants of Apamea spared the Jews who lived in their midst and would not suffer them to be murdered or led into captivity.

[13] Since Apamea virtually belonged to Rabbinic Palestine, the first-fruits brought by Ariston from that town were accepted for sacrifice in Jerusalem.

As a result of the civil war in Syria, the ancient city has been damaged and looted by treasure hunters.

[22][23] In April 2017, Al-Masdar News published satellite photographs revealing the site was covered in hundreds of holes dug by treasure hunters seeking ancient artifacts.

[24] The Great Colonnade was situated along the main avenue of Apamea and ran for nearly 2 kilometres (1.2 mi), making it among the longest in the Roman world.

[26] The colonnade passed through the centre of the city and several important buildings were clustered around it, including the baths, the agora, the Temple of Tyche, the nymphaeum, the rotunda, the atrium church and the basilica.

[32] Under the Byzantine Empire the theatre's drainage basin was restructured and a qanat was built through the middle of the lower stage.

[35] Much of its structure is in ruins due to architectural collapses and extensive quarrying in later epochs,[36] and only one-eighth of the site has been exposed so far.

[37] This mosaic, now in the Cinquantenaire Museum, Brussels, was discovered in 1935 in the reception room of what was probably the palace of the Roman governor of the province of Syria Secunda.

An inscription at the entrance states: "During the most beautiful Apellion, the triclinium was rebuilt in the month Gorpiaios, third indict, in the year 851" (September, 539 AD).