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This article develops the concept of infrastructural exclusion as a form of urban inequality through the case of the origins of the food desert in Philadelphia. Infrastructural exclusion refers to the reorganization of spatial and material interdependence into a semi-autonomous and path-dependent force that separates resources from those reliant on them. Building on archival research, it emphasizes how social problems arise out of taken-for-granted relationships between urban development, population settlements, and distribution systems. Grocery chains were interdependent with urban neighborhoods in the early 1900s, but they came to participate in a fiercely competitive industry during a precarious period of urban decline, suburban growth, and changes in transportation systems. New industry conventions about profitability, involving higher-volume supplies and lower transaction costs, became embedded into the sociotechnical infrastructure. The reorganization of infrastructural interdependence as a semi-autonomous force constrained local business decision-making, led to high rates of financial insolvency, and contributed to the overall decline of urban grocery markets. This approach to infrastructural exclusion provides insights into the causes of a unique form of urban inequality.