The tire-pavement interaction has become an important research topic in recent years as the road transportation system and automobile industry develop. The distribution of contact stress between tires and asphalt pavement caused by traffic load is nonuniform. Furthermore, the asphalt mixture is a typical heterogeneous composite material, consisting at the microscale of aggregates, asphalt binder and air voids. However, much of the previous research has tended to focus on uniform-loaded pavement structure, which is comprised of homogeneous asphalt mixture. In this study, the inhomogeneous contact stress was applied on the macroscale finite element pavement model to study the influence of footprint on the mechanical properties of the asphalt pavement. The effect of tire contact stress on asphalt mixtures was investigated using a coupling method between the pavement model and a microscale model of asphalt mixture. This proposed algorithm is capable of simulating the impact of traffic load on the pavement structure and the asphalt mixture in real situations. It is useful for gaining a better understanding of the deformation processes that occur within the asphalt mixture under the real traffic load, which cannot be derived from the conventional laboratory tests and thus is beneficial to the pavement design.