The earliest historical records of Mesopotamian states of the last centuries of the third millennium BCE document their close interaction with peoples and polities in the hills and mountains of the Zagros and Trans-Tigridian region. The origins and sociopolitical organization of these peoples remain poorly understood largely due to the limited archaeological fieldwork undertaken in this region. However, numerous Mesopotamian administrative records, literary sources, and archaeological evidence for exchange document a long history of a symbiotic, but frequent antagonistic, relationship between the lowland states and highland peoples. Surveys and excavations in the Zagros and Trans-Tigridian region have struggled with identifying the material culture of the Early Bronze Age, giving the impression of a largely abandoned landscape perhaps inhabited by a few pastoral nomadic tribes. New fieldwork at the site of Kani Shaie in Iraqi Kurdistan conducted in the context of this dissertation between 2012-16 and an analysis of the unpublished survey and excavation records of the Mahi Dasht Survey Project undertaken between 1975-78 in Kermanshah, Iran, by L. Levine of the Royal Ontario Museum, has revealed previously unrecognized Early Bronze Age local material culture, especially in the form of indigenous painted ceramic traditions and administrative practices. This allows a reevaluation of the Early Bronze Age in the Zagros region, which demonstrates that the region remained densely inhabited throughout the third millennium BCE albeit with significant shifts in the organization of interregional interaction. Following the collapse of the Late Chalcolithic directional interaction network that had connected distant settlements and allowed the spread of the “Uruk” material culture throughout the fourth millennium BCE, the first centuries of the Early Bronze Age saw the emergence of distinct cultural zones occupying different altitudinal-ecological regions (plains; hills; intermontane valleys). These different societies formed an interaction sphere in which intersocietal exchange of resources, ideas, and perhaps people, occurred periodically at border sites located in the interstitial zones between different landscapes. Finally, in the second half of the third millennium, Mesopotamian states again sought to establish direct contact with distant lands to obtain resources, thereby establishing a new directional network that profoundly changed power relationships and indigenous social structures.