Vehicle lightweighting and advanced powertrains, including hybrid electric systems and high efficiency engines, have the potential to increase fuel economy and decrease life cycle energy and greenhouse gas (GHG) emissions. However, the energy and GHG impact over the entire vehicle life cycle is dependent on the energy and emissions required to produce lightweight materials and fuels. Recent work has used life cycle assessment (LCA) to evaluate diverse vehicles and fuels using a novel design harmonization technique. The current work describes this approach in further detail and provides an example of its application for a moderate lightweighting scenario for an internal combustion vehicle (ICV), hybrid electric vehicle (HEV) and plug-in hybrid electric vehicle (PHEV). This type of apples-to-apples comparison is enabled by functional equivalency metrics, which are defined as part of the design harmonization technique and held constant across all vehicles. The technique also establishes a process to account for mass and materials differences for conventional and hybrid electric vehicles. For instance, the structural support that is required for heavier powertrains is assessed and found to be 0.2-0.3 kg per unit increase in powertrain mass. Once baseline vehicle models are established, lightweight versions are developed using vehicle teardown data and mass compounding models, including secondary mass reductions and powertrain resizing. From this information, fuel economy and life cycle energy and GHG emissions can be determined for the baseline and lightweight vehicles. The design harmonization technique developed in this work establishes a framework to evaluate the combined impact of advanced powertrains and vehicle materials to reduce life cycle energy and GHG emissions.