This work assesses the potential of electrified vehicles and mass reduction to reduce life cycle energy and greenhouse gas (GHG) emissions. Life cycle assessment (LCA) is used to account for processes upstream and downstream of the vehicle operation, thereby incorporating regional variation of energy and GHG emissions due to electricity production and distinct energy and GHG emissions due to conventional and lightweight materials. Design harmonization methods developed in previous work are applied to create baseline and lightweight vehicle models of an internal combustion vehicle (ICV), hybrid electric vehicle (HEV) and plug-in hybrid electric vehicle (PHEV). Thus, each vehicle is designed to be functionally equivalent and incorporate the structural support required for heavier powertrains. Lightweight vehicles are designed using body-in-white (BIW) mass reduction scenarios with aluminum and advanced/high strength steel (A/HSS). For the mass reduction scenarios considered in this work, results indicate that the greatest life cycle energy and GHG emissions reductions occur when steel is replaced by aluminum. However, since A/HSS requires less energy to produce as compared to aluminum, the energy and GHG reductions per unit mass removed is greatest for A/HSS. Results of the design harmonization modeling method show that 0.2–0.3kg of structural support is required per unit increase in powertrain mass, thus extending previous methods.