Greenhouse gas (GHG) accounting at the city-scale is confounded by the relatively small spatial scale of cities compared to their surrounding commutersheds, watersheds and electric power distribution networks. Consequently, important infrastructures serving cities such as regional mass transit, water supply, electric power supply, airline travel, etc., are artificially truncated at the city's geopolitical boundary. Thus, models that strictly evaluate direct energy use and GHG emissions within city boundaries do not fully represent the impact of urban activities on the larger environment. This presentation describes an emerging methodology for GHG emissions accounting and carbon footprint-ing at the city-scale that integrates infrastructures with urban metabolism and with industrial ecology to overcome the boundary challenges listed above. The methodology yields a trans-boundary infrastructure-based supply chain GHG emissions footprint for cities. Field-tested in eight US cities, the infrastructure-based GHG emissions footprint is found to track well with national benchmarks, and to stimulate innovative low-carbon infrastructure design strategies and policies in buildings, transportation, energy, water, waste and food sectors. Select examples of sustainable infrastructure research projects that reduce the GHG emissions footprint of cities will be discussed. The footprint concept also anchors an inter-disciplinary framework for study of sustainable city-systems by linking water-, energy- and carbon-footprints of cities with various social actors - e.g., individual users, infrastructure designer-operators, firms/businesses, and policy actors - who shape urban infrastructures toward sustainability goals. The framework is illustrated via quantitative analysis of carbon stabilization wedges for US cities, addressing the role of the social actors in various infrastructure interventions. The framework stimulates ongoing cross-disciplinary research across infrastructure design, environmental engineering, industrial ecology, urban planning, public policy, health and behavioral sciences, essential for building sustainable city-systems of the future.