This dissertation explores the formation of an economic region within the wider context of the Roman Mediterranean economy in a study of southern Italy from the 1st-6th c. CE. This dissertation contributes to the study of the Roman economy by advancing a methodology for the identification and study of regional systems, and by offering a new interpretation of the southern Italian economy during this period. My goal in this project is to understand the role of rural economic processes in creating a regionally connected system across space and through time, and the implications of such connections for the long term economic experience of southern Italy in particular. How did a regional system form in southern Italy? How might regional economic connections in rural contexts have contributed to the stability of southern Italy as it advanced from the imperial period into late antiquity? Southern Italy provides a revealing case study for exploring these economic processes because of the stability, perhaps prosperity, of its economic system into late antiquity, a period of great change in the larger Mediterranean economy. I take a long-term approach and argue that the strength of its regional connections played a fundamental and foremost role in sustaining a stable southern Italy economy, laid down in part before the onset of late antiquity. Evidence comes from a wide geographic area in southern Italy, composed of the modern-day provinces of Puglia, Basilicata, Campania and the Molise, and includes data from excavated and surveyed villa, village and farm sites. It offers information on settlement patterns, the role of transhumance pastoralism, production strategies, and patterns of consumption, all important components of economic life in these rural landscapes, treated in four separate chapters of this dissertation. I contextualize this material and textual evidence within its wider landscape, among routes of connection, urban places, and the natural environment to create a comprehensive, layered picture of how sites, their production activities and the movement of people and goods contributed to building this regional system over time. This dissertation demonstrates that a strong regional economy, formed through rural economic flows, was important for creating stability in southern Italy over time, even in light of the transformations in the Mediterranean economy in the later empire. From the perspective of studies on the Roman economy in general, this dissertation argues for the importance of interrogating mid-scale spatial systems of organization to understand better how the Roman economy functioned.