The historiography of the Syrian Desert—which covers parts of present-day Syria, Iraq, Jordan, and Saudi Arabia—generally considers this desert region as one that separates as much as it connects different territories. In the late Ottoman period, merchant caravans, Bedouins, pilgrims and other travellers regularly crossed the desert. Relying on these existing social and infrastructural networks, travellers made their way across the desert in greater numbers in the interwar period due to the spread of motorized transport. While a growing number of scholars have paid attention to regional patterns of mobility in the interwar Middle East, the development of a region-wide motor transport infrastructure remains understudied. This paper traces the beginnings of the Baghdad-Damascus route by examining the various components of the new transport system: automobiles, roads and tracks, transport companies, and government support. In doing so, it attempts to examine the co-production of technology, (imperial) politics, and geography. In the opinion of contemporary observers and actors, the opening of the Baghdad-Damascus motor route was a ‘conquest of the desert’, whose success they attributed to the rationality and commercial ability of the ‘pioneers’ of motor transport as well as to modern technology. This narrative overlooks the many ways in which desert topography played a part in the development of transdesert transport services in the 1920s. In contrast, I argue that the topographical features of the Syrian Desert (re)shaped the various components of the infrastructural system as well as the interests of the French and British Mandate powers in the region First, the paper seeks to demonstrate that the desert surface affected the transport infrastructure: the type of vehicle, the route, the type of traffic carried by road operators, and the material structure. In doing so, the paper does not seek to give in to the narrative that the desert ‘resisted’ its ‘conquest’ by the automobile, but to show how the various actors adapted to the topographical constraints, accommodated them, and even developed new forms of automobility. Second, the paper examines the ways in which the topography of the region played a role in the Franco-British relationship in the Eastern Mediterranean. As a trans-imperial or trans-Mandate route, the Baghdad-Damascus motor route offers a privileged site for examining cases of cooperation and rivalry between them.