Heavy-duty vehicles (HDVs) impose pollution on the local environment, degrade transportation infrastructure, and contribute to global warming through greenhouse gas emissions (GHGs). HDVs are also critical to a variety of diverse vocations, including school and urban mass transit, refuse collection, goods distribution, and short and long-haul freight movements. In the transportation sector, the focus of emissions reductions strategies has been the deployment of new technologies, including: emissions control devices, vehicle efficiency upgrades, zero emissions vehicles, and low-carbon fuels, such as electricity, hydrogen, and biofuels. Yet, neither the emissions from these technologies nor their impacts on pollution are well understood. Not only is consideration of the entire lifecycle of both vehicles and fuels critical for comparing emissions across technologies, a systems perspective is required to quantify tradeoffs and identify opportunities for leakage in these pollution control strategies. This research develops and refines methods of assessing the life cycle environmental impacts of transportation technologies, strategies, and policies. It offers a novel framework for assessing life cycle emissions abatement potential under uncertainty. The practical contribution of this research is to inform on-going investments in advanced HDVs, low-carbon fuels, and sustainable freight technologies. The research also contributes to the deficient body of empirical knowledge by using life cycle assessment, life cycle costing, and numerical analysis to estimate duty-cycle specific life cycle inventories and life cycle abatement costs of key pollutants for several HDV and fuel pathways.