The city of Apamea in Phrygia was founded by Antiochus I Soter (280–261 BCE) as part of a scheme to strengthen the Seleucid hold on Asia Minor, to facilitate trade and to protect the highways. It was one of a series of garrison-cities and was built at a point of strategic importance on the Great Southern Highway. Antiochus I Soter founded the city on a plateau on either side of the Marsyas River by moving the inhabitants of nearby Celaenae into his newly created city. Celaenae itself was a large and prosperous city with a long history. Under Persian rule, Celaenae became the principal royal seat in Phrygia and a residence of the satraps. After Alexander conquered the city, it was designated as the Greek Capital of Inner Anatolia.

At the beginning of the common era, Apamea was the second most important market and distribution centre in Asia Minor owing to its geographical location. The city commanded the cut in the mountain range through which the Southern Highway climbed to the plateau of Central Anatolia, making it the commercial junction through which wealth-laden traffic passed to the East. Roads of commercial importance also led to Western Phrygia and into Pisidia. Its position meant it was a strategic city with regard to defence.