We explore settlement structures and hierarchy found in different archaeological periods in northern, specifically the Khabur Triangle (KT), and southern Mesopotamia (SM) using a spatial interaction entropy maximization (SIEM) modeling and simulation method. Regional settlement patterns are investigated in order to understand what feedback levels for settlement benefits, or incentives, and abilities to move or disperse between sites in a landscape and period could have enabled observed settlement structures to emerge or be maintained. Archaeological and historical data are then used to interpret the best results. We suggest that in the Late Chalcolithic (LC) and first half of the Early Bronze Age (EBA), the KT and SM appear to have comparable urban patterns and development, where settlement advantage feedbacks and movement are similarly shaping the two regions for those periods. Within period variations, such as restrictions to population diffusion or movement in the EBA, are possible. In the KT during the Middle Bronze Age (MBA), multiple centers begin to emerge, suggesting a lack of social cohesion and/or political fragmentation. This is similar to SM in the MBA, but we also see the emergence of a single, dominant site. In the Iron Age (IA), movement in the KT likely becomes the least constrained in all assessed periods, as socio-political cohesion facilitates this process, with small sites now the norm and dominance by one state over the region is evident. For the same period in SM, a single site (Babylon) obtains significant settlement advantages relative to its neighbors and easy movement enables it to become far larger in size and likely socially, economically, and politically dominant. Overall, the results demonstrate that the method is useful for archaeologists and social theorists in allowing them to compare different archaeological survey results, with varied spatial dimensions and diachronically, while providing a level of explanation that addresses empirical settlement patterns observed.