Economic geographers correctly note that regional variations in economic activity and population agglomeration are always the result of self-reinforcing processes of resource production, accumulation, exchange, and innovation. This article proposes that essentially similar forces account for the emergence of the world's earliest cities in the alluvial lowlands of the Tigris and Euphrates rivers (Southern Mesopotamia), sometime during the second half of the fourth millennium BC.That emergence of early cities in the southern Mesopotamian alluvium must be understood in terms of the unique ecological conditions that existed across the region during the fourth millennium, and the enduring geographical framework of the area, which allowed for the efficient movement of commodities via water transport and facilitated interaction between diverse social units alongside natural and artificial river channels. These conditions promoted evolving long-term trade patterns that, inadvertently, differentially favored the development of polities in the southern Mesopotamian alluvium over contemporary societies in neighboring regions.More specifically, my contention is that by the final quarter of the fourth millennium the social and economic multiplier effects of trade patterns that had been in place for centuries - if not millennia - had brought about substantial increases in population agglomeration throughout the southern alluvial lowlands. Concurrent with these increases, and partly as a result of them, important socio-economic innovations started to appear in the increasingly urbanized polities of southern Mesopotamia that were unachievable in other areas of the Ancient Near East where urban grids of comparable scale and complexity did not exist at the time. Most salient among these innovations were (1) new forms of labor organization delivering economies of scale in the production of subsistence and industrial commodities to southern societies, and (2) the creation of new forms of record keeping in southern cities that were much more capable of conveying information across time and space than the simpler reckoning systems used by contemporary polities elsewhere. These innovations furnished southern Mesopotamian polities of the fourth millennium with what turned out to be their most important competitive advantage over neighboring societies. More than any other factor, they help explain why complex regionally organized city-states emerged earlier in southern Iraq than elsewhere in the Near East, or the world.