One of the global community’s most significant contemporary challenges is the need to satisfy growing energy demand, while simultaneously achieving very significant reductions in the greenhouse gas (GHG) emissions associated with the production, delivery, and consumption of energy. The energy sector is transforming via the convergence of power, transportation, and industrial sectors and inter-sectoral integration. To assess the level of decarbonization achieved through this change, one needs to study the carbon footprint of the energy system as a whole. Here, we present a novel, system-scale energy analysis tool, the Sustainable Energy System Analysis Modelling Environment (SESAME), to assess the pathway- and system-level GHG emissions of today’s changing energy system. The underlying analytic tool constitutes more than a thousand individual energy pathways. SESAME provides a consistent platform to estimate life cycle GHG emissions of all stages of the energy sector. Furthermore, the system representation is embedded into the tool for power and transportation sectors. The developed novel architecture, and implications of energy choices for example scenarios (vehicle fleet projections for US and generator-level hourly power generation) are presented to demonstrate SESAME’s high-resolution analysis capabilities. Impact of operational variations such as partial loading of power generation units and technology choices, such as treatment of the same crude oil in different refinery configurations, is explored.