The proper understanding of tire-pavement interaction is important for the accurate analysis of load-induced stresses and strains in the pavement structure. This dissertation focuses on the analysis of the mechanism of tire-pavement interaction and the effect of tire-pavement interaction on pavement responses using a decoupled modeling approach. First, an air-inflated three-dimensional (3-D) finite element (FE) tire model was built and the interaction between a tire and a non-deformable pavement surface was simulated. The tire is modeled as a composite structure including rubber and reinforcement. The steady-state tire rolling process was simulated using an Arbitrary Lagrangian Eulerian (ALE) formulation. The developed tire-pavement interaction model is used to evaluate the mechanism of load distribution at the tire-pavement interface under various tire loading and rolling conditions. After that, a 3-D FE model of flexible pavement was developed to analyze pavement responses under various loading scenarios. This model utilizes the implicit dynamic analysis, simulates vehicular loading as a continuous moving load, and incorporates 3-D contact stresses at the tire-pavement interface. In the pavement model, the asphalt layer is modeled as a linear viscoelastic material and the granular base layer is modeled as a nonlinear anisotropic material. The FE pavement model was used to analyze critical pavement responses in thin and thick asphalt pavements considering different damage mechanisms. This dissertation concludes that knowledge of tire-pavement contact stress distributions is critical for pavement response prediction. Most importantly, the non-uniform distribution of vertical contact stresses and the localized tangential contact stresses should be considered in the mechanistic-empirical pavement design. The contact stress distributions at the tire-pavement interface are affected by vehicle loading (wheel load and tire inflation pressure), tire configuration (dual-tire assembly and wide-base tire), vehicle maneuvering (braking/acceleration and cornering), and pavement surface friction. Therefore, pavement damage should be quantified using accurate loading inputs that are represented by realistic tire-pavement contact stress distributions. Thin and thick asphalt pavements fail in different ways. Multiple distress modes could occur in thin asphalt pavements, including bottom-up fatigue cracking and rutting in each pavement layer. It was found that the interaction between the viscoelastic asphalt layer and the nonlinear anisotropic granular base layer plays an important role for the stress distribution within a thin asphalt pavement structure under moving vehicular loading. In thick asphalt pavements, near-surface cracking is a critical failure mechanism, which is affected by the localized stress states and pavement structure characteristics. Particularly, the effect of shear stress on the formation of near-surface cracking at multi-axial stress states is important and can not be neglected, especially at high temperatures.