To fulfill the goal of United Nation’s Paris agreement and become carbon neutral by 2050, all signatory countries and organizations must decarbonize every sector of its economy, including transportation by the year 2050 on a life cycle basis. While energy is the largest greenhouse gas (GHG) emitting sector globally, transportation is the fourth largest emitting sector, contributing to 15% of the global GHG emissions in 2019. The transportation sector includes five different modes: Aviation, Marine, On-road, Off-road, and Rail, which further have several types of vehicle/equipment under each of them, that are utilized differently over their life cycle. Within the United States (US), 80% of the total emissions from the transportation sector are from the on-road sector, i.e., light duty vehicles and heavy-duty trucks. This makes it an important sector for decarbonization with a techno-economical approach, that reduces emissions at lower costs for each vehicle type. Therefore, this chapter discusses the strategy to calculate life cycle GHG emissions and life cycle cost of on-road transportation modes in the US for various vehicle types. Additionally, the chapter includes dedicated analysis and discussion on electricity and hydrogen’s role in decarbonizing the transportation sector.