Abstract Energy security and climate change are long-term challenges for the transportation sector in the United States. Natural gas use in vehicles may reduce the dependence of the transportation sector on petroleum fuels, but provides only a marginal reduction in well-to-wheels (WTW) greenhouse gas (GHG) emissions. Improvement in vehicle efficiency provides a proportional reduction in both petroleum use and GHG emissions. The use of conventional hybrid electric vehicles reduces WTW petroleum use and GHG emissions by 33% compared to gasoline internal combustion engine vehicles (ICEVs). Using fossil fuels-derived natural gas for electricity and hydrogen production reduces WTW GHG emissions of battery electric vehicles and fuel cell electric vehicles by 56% and 39%, respectively, compared to gasoline ICEVs. Reductions in GHG emissions in excess of 80% compared to conventional gasoline ICEVs can be achieved with the use of renewable sources, such as wind, solar, and biomass, as energy feedstocks for electricity and hydrogen production.