<p>Accurate evaluation and prediction of fatigue performance are crucial for extending the service life of asphalt pavements. Asphalt materials exhibit complex behavior influenced by varying temperatures and loading conditions, with aging being a key factor in the early deterioration of pavement structures. Alongside aging, mix design factors, individually or combined, also play a significant role in the fatigue cracking performance of bituminous mixtures. Despite recent advances, the complex relationship between aging and mix design factors affecting asphalt pavement fatigue performance remains not fully understood. Additionally, a standardized testing procedure has yet to be established. This research investigates the impact of aging on the fatigue resistance and long-term performance of three dense-graded asphalt mixtures while also considering the influence of mix design variables. To assess fatigue performance, the recently developed ASTM D8458-22 three-point bending cylinder test in conjunction with the viscoelastic continuum damage model was employed. The study further incorporates mechanistic-empirical analyses to forecast the long-term behavior of three distinct pavement designs under various aging scenarios. The results indicate a clear correlation between aging duration and the decline in fatigue performance of asphalt mixtures. Several critical mix design factors, including aggregate gradation, binder content, and performance grade, significantly influence the rate of aging. Additionally, the mechanistic-empirical analysis reveals an interesting difference in the effects of aging. While it reduces bottom-up fatigue performance, making the mixture more susceptible to fatigue cracking from the lower layers, it simultaneously enhances resistance to top-down fatigue cracking, which originates at the pavement surface.</p>