Assessing the sustainability of products is an intricate task that requires a thorough understanding of the underlying supply chains. Prominent challenges are the integration of the environmental, the economic, and the social dimension of sustainability as well as the consideration of spatial heterogeneity with regard to technology, environment, markets, and society. This paper proposes a novel modeling approach based on activity analysis to facilitate spatially differentiated sustainability assessments of global supply chains. The production and transportation activities in the supply chain and the exchanges between activities and their natural, economic, and social environments are formalized by means of activity vectors. Linking the activities and exchanges to specific locations allows for the calculation of regionalized sustainability indicators. The approach is used to analyze the environmental, economic, and social impacts of lithium-ion batteries. The comparison of alternative supply chain configurations with the spatially differentiated approach reveals that the assessment results differ significantly from those of the global average supply chain. These insights offer new opportunities to advance the design of sustainable supply chains.