The valley of the middle Orontes is not only extremely fertile, it is also flat, so that armies can easily encounter each other. The river has seen many military engagements. The most famous of these is the Battle of Kadesh in 1274 BCE, in which the armies of the Hittite king Muwatalli II and pharaoh Ramses II clashed; the latter won a tactical victory, but had to admit that the valley was taken over by the Hittites. Many other encounters have been recorded.
In c.300 BCE, Seleucus I Nicator founded three cities along the river: Apamea, Antioch, and Seleucia. Antioch became the main residence of his dynasty and the capital of the Roman province Syria. Today, it is a lively city, with a splendid museum full of ancient mosaics. I moved and expanded my page on Antioch; it is now here. Only 220 pages to go.