Cities consume most of the energy used worldwide and are the largest emitters of greenhouse gases (GHGs) that cause global warming, mainly from the road transport sector. In megacities, the light vehicle fleet is responsible for most of the emissions in the sector. Among this fleet, light commercial vehicles (CVs), which have grown to support instant delivery services demand, are also responsible for emissions and traffic congestion. Due to the urgency to reduce transport impacts, emission mitigation strategies are required. Aligned with this aim, this article evaluates GHG emissions along the entire process of energy production, called the operating trajectory, and also known as Well-To-Wheel (WTW), in four combinations of transportation modes for last-mile delivery services, using light CVs, such as electric or diesel vans, and electric cargo bikes (E-bikes). The analysis is firstly conducted in a local area of Mexico City and subsequently compared to other countries around the world. In this respect, the main result of this article shows that in the case study conducted in the Metropolitan Zone of the Valley of Mexico, the energy consumption of a given route for an electric van combined with E-bikes generates 24% less GHG emissions than a diesel van combined with E-bikes. Therefore, the achievement of effective mitigation strategies for GHG emissions reduction through vehicle electrification requires WTW emission analysis and quantification, optimal route design, a combination of sustainable transport modes and clean energy generation.