Most of these cities once flourished in the valley of the Orontes River (Nahr al-‘Asi today); many of them were prominent cities from the Seleucid period, through the Roman, and into the Byzantine eras.
East Anatolian Fault, shown in the map, running along and under the Taurus Mountains and up into the Caucasus; it is, and has long been, one of the world's most active earthquake zones. Many of these cities were destroyed multiple times by earthquakes.
Another factor was the rise of Islam. By the end of the Islamic conquests, this region of Syria was captured by Islam; the Byzantine Emperor Heraclius reportedly said, departing Antioch for Constantinople, according to the Arab historians at least, "Farewell Syria! And what a wonderful country this is for the enemy." Under the Umayyad Caliphs, Damascus became the capital of the Caliphate, shifting the center of gravity in Syria from the north, Antioch, to the south, Damascus.
And therein lies the real key: with the dimming of Antioch's star, the hinterland of Antioch, once a rich country, declined. Antioch was a city of half a million in Classical times, one of the four largest in the Roman Empire after Rome, Alexandria, and Ephesus (later eclipsed by Constantinople). At the gateway to Anatolia (on the route to the Cilician Gates), it also stood at the western terminus of the Silk Road to the East. It was one of the great Patriarchates of early Christianity, where Peter was the first bishop (preceding his move to Rome), and where, according to Acts 11:26, "The disciples were called Christians first at Antioch."
Overshadowed by Damascus, Antioch declined; it was still a great city at the time of the Crusades, but a series of earthquakes and the disruption of the Silk Road during the Mongol Conquests helped seal its eclipse.
Antioch is not a "dead city," but it is a shadow of its former self. Part of Turkish territory since 1939, after the French Mandate in Syria first declared the former Sanjaq of Alexandretta, known to Turks as the Hatay, as an independent Republic of Hatay in 1937, annexed by the Turkish Republic in 1939. Known as Antakya in Turkish, it is still the seat of Hatay Province, though overshadowed by the seaport of Iskenderun (Classical Alexandretta). Today it has a couple of hundred thousand people, fewer than half its population two millennia ago. It is also cut off from its traditional hinterland by the Turkish-Syrian border, which is not far to the east of Antioch. It is a quiet town on the Orontes,
To add insult to injury, even its once dominant role in Christianity has been diluted. Not only is there still a Patriarch of Antioch, there are five. But three are based in Damascus, one in Beirut and one in Bkerke, Lebanon: in other words, none of them in ancient Antioch, though they all still bear the title.
The Patriarchs of Antioch represent the Eastern (Antiochene) Orthodox (whose present see is in Damascus), Syriac Orthodox (sometimes called "Jacobite") (Damascus), Maronite Catholic (Bkerke), Melkite Catholic (Damascus), and Syriac Catholic (Beirut) Churches. The last three are all in union with Rome, the Antiochenes are "Eastern Orthodox" in communion with Constantinople, and the Syriac Orthodox are Oriental Orthodox in loose communion with the Copts and Armenians. There used to be a Latin Catholic Patriarch of Antioch as well, but the title lapsed in the 20th Century.
While we are on the subject of Antiochene Christianity, I guess I should reveal what the photo at the top is. One of the best known figures in this part of Syria in late Antiquity was Saint Simeon Stylites, a pious monk who lived roughly 390-459 AD, and is renowned for living for 39 years sitting at the top of a pillar. It was a new form of asceticism, and his followers would bring him bread and goat's milk. Not content with his first pillar, he acquired higher and higher ones, the last being some 15 meters tall, the food raised by some sort of block and tackle mechanism.
The image at left, a 6th Century depiction from the Louvre (from the Wikipedia page) may not be precisely historical. I have my doubts about the snake. But apparently Simeon Stylites became so famous on his pillar in the desert east of Antioch that pillar-sitting became quite the fashion among anchorites for a time. And of course, once he passed on, his pillar became a pilgrimage site, with the town of Telanissos flourishing from the pilgrimage trade. But the monastery and shrine built around his pillar is still there, in ruins, between Aleppo and Antioch, inside Syria only a few kilometers from the Turkish border. Saint Simeon Stylites is known in Arabic Chtistianity as Mar Sem‘an al-‘Amudi, and the Church of Saint Simeon complex is known as Deir Sem‘an (the Monastery of Simeon) or Qala‘at Sema‘an (Castle or Citadel of Simeon). That pedestal with a round rock on it at the top is what remains after 15 centuries of pilgrims chipping away for souvenirs of the Saint's pillar. (Also see Ibn Battuta's link from the comments.)
All photos from Wikimedia Commons.