The fuel consumption of heavy-duty trucks varies with several factors, such as driving style, traffic and weather conditions. This paper attempts to establish an effective simulation of fuel consumption while driving. First, the actual driving mode conditions were investigated with a heavy-duty truck and statistically analyzed to derive empirical equations. Second, vehicle driving resistance and performance were measured to improve simulation accuracy. The resulting computational simulation analysis based on the above experimental information and theoretical background enables more accurate prediction of the fuel consumption and drivability of heavy-duty trucks.