As lightweight materials and advanced combustion engines are being used in both conventional and electrified vehicles with diverse fuels, it is necessary to evaluate the individual and combined impact of these technologies to reduce energy and greenhouse gas (GHG) emissions. This work uses life cycle assessment (LCA) to evaluate the total energy and GHG emissions for baseline and lightweight internal combustion vehicles (ICVs), hybrid electric vehicles (HEVs) and plug-in hybrid electric vehicles (PHEVs) when they are operated with baseline and advanced gasoline and ethanol engines. Lightweight vehicle models are evaluated with primary body-in-white (BIW) mass reductions using aluminum and advanced/high strength steel (A/HSS) and secondary mass reductions that include powertrain re-sizing. Advanced engine/fuel strategies are included in the vehicle models with fuel economy maps developed from single cylinder engine models. Results show that while the ethanol engine has the highest efficiency and therefore, highest MPGe, the increased energy required to produce ethanol outweighs this benefit. The most life cycle energy and GHG reductions occur with aluminum, but the energy and GHG reduction per unit mass removed is greater for A/HSS. For the scenarios considered in this work, the least life cycle energy and GHGs are obtained with a lightweight PHEV with an aluminum BIW and advanced gasoline engine. Overall, results show that advanced gasoline and ethanol engines and lightweight materials provide complimentary benefits for conventional and electrified vehicles and will reduce life cycle energy and GHG emissions while playing a key role in meeting future CAFE standards.