Abstract: Pavement unevenness affects the vehicle operating cost, speed, riding comfort, safety, pavement service life and etc. The current mechanistic-empirical (M-E) design procedure of asphalt pavements is based on the computational model of a flat pavement instead of uneven pavement as it is the case in reality. In this paper, a tire-pavement-interaction FE model is developed to investigate the influence of pavement unevenness on the mechanical responses of asphalt pavements. For both winter and summer conditions, the strain at the bottom of the asphalt layer due to the tire load is found to decrease as the wavelength of the unevenness increases. Moreover, the strain is larger at lower speeds and decreases as the speed increases. It is found that the stress levels are higher in summer conditions than under winter conditions for the same pavement irrespective of wavelength. The fatigue life increases with increase in speed of the tire for a pavement and also increases with increase in the wavelength of the pavement unevenness. The results indicate that pavement unevenness significantly influence the mechanical responses of asphalt pavements and thus influences the service life of asphalt pavements. As a result, the current M-E design algorithm of asphalt pavements should be modified to consider the pavement unevenness to allow better design processes for asphalt pavement.