Using chronological and anthropological methods, this article examines the stages of human settlement and exploration in the northeastern Azov region, spanning from the Mius River valley to the Mertvy Donets River. Using the latest archaeological and historiographic data, the history of the region is traced from the Early Paleolithic era through classical antiquity, the Middle Ages, and modern times. The impact of climate change and geological processes on human communities is demonstrated. The article also demonstrates the constant and multifaceted connections between the population of this territory and those of nearby and more distant regions of Eurasia. The emergence of the northernmost Greek colony of early antiquity in this region, the role of the Greek presence in the region during classical antiquity, and the significance of Greek historiography for modern humans are considered. The long line of peoples who passed through and lived in the region, as well as the key features of their culture, economy, and politics, are identified. The factors contributing to the region’s unique appeal and the persistent struggle between peoples and states for the possession of local resources in various historical periods are revealed. The dramatic saga of Russian penetration into the region is illustrated, beginning in the early Middle Ages and continuing until the region’s consolidation within the Russian state. It is concluded that Russia ensured peace and prosperity in the Azov region through its consistent, rational, and just policies.