Smart technologies enabling connection among vehicles and between vehicles and infrastructure as well as vehicle automation to assist human operators are receiving significant attention as a means for improving road transportation systems by reducing fuel consumption – and related emissions – while also providing additional benefits through improving overall traffic safety and efficiency. For truck applications, which are currently responsible for nearly three-quarters of the total U.S. freight energy use and greenhouse gas (GHG) emissions, platooning has been identified as an early feature for connected and automated vehicles (CAVs) that could provide significant fuel savings and improved traffic safety and efficiency without radical design or technology changes compared to existing vehicles. A statistical analysis was performed based on a large collection of real-world U.S. truck usage data to estimate the fraction of total miles that are technically suitable for platooning. In particular, our analysis focuses on estimating “platoonable” mileage based on overall highway vehicle use and prolonged high-velocity traveling, and established that about 65% of the total miles driven by combination trucks from this data sample could be driven in platoon formation, leading to a 4% reduction in total truck fuel consumption. This technical potential for “platoonable” miles in the United States provides an upper bound for scenario analysis considering fleet willingness and convenience to platoon as an estimate of overall benefits of early adoption of connected and automated vehicle technologies. A benefit analysis is proposed to assess the overall potential for energy savings and emissions mitigation by widespread implementation of highway platooning for trucks.