This paper examines the changing geopolitical role of Syria in the Eastern Mediterranean after the Ottoman conquest of 1516. The shift in Syria’s borders that took place with the change of dynasty made significant alterations in Syria’s geopolitical and economic position. From a frontier province connected rather tenuously to Egypt and Arabia under the Mamluks, it became under the Ottomans a central hub for military affairs and for commercial and cultural exchange, the focus of a newly Ottoman Mediterranean. This framework connects the Mamluk and Ottoman periods in the region, provides an alternative to the nationalistic “conquest, oppression, resistance” framework under which so much research has been conducted, and makes a contribution to the history of global change and interaction. The paper seeks to do two things: one, to enumerate significant areas of change in Syria that this geopolitical shift affected and discuss how existing research, old and new, illuminates these areas. The elimination of borders, changes in trade patterns, new or newly bustling roads and routes, the shift in the main route of the hajj and its results, population movements, new constructions erected to accommodate these changes, cultural contacts and the production of new literatures and new legal interpretations are all reinterpreted as resulting from the change in Syria’s geopolitical position. Secondly, I want to highlight unanswered questions raised by this approach and address one of them, the economic expansion in Syria brought about by the conquest, which is often referred to but not actually studied. Using financial records included in tax surveys and reports from the province, collected from the Ottoman archives, I will examine how the amounts and proportions of revenue from different activities in the province altered during the sixteenth century and analyze that in the light of what we have from other sources, such as travelers’ reports and histories. The purpose is to verify the increase and which sectors of the population benefited from it, and to evaluate Syria’s worth to the empire and the empire’s worth to Syria.