The application of tunnel waste slug, which is employed as road base fill, can effectively reduce resource wastage and environmental pollution. However, when it is studied as a continuous medium by means of finite element methods, there are inherent limitations. Moreover, in discrete element simulations of granular materials, the influence of mesoscopic parameters on the macroscopic mechanical properties of the material remains unclear. Based on triaxial compression tests and numerical simulations, this study employs the orthogonal analysis to control parameter variations, so as to reveal the correlation between granular mesoscopic parameters and macroscopic mechanical properties. Thus the impact of mesoscopic parameters on the road mechanical characteristics of graded tunnel waste slug is clarified. The results indicate that among the mesoscopic parameters, shear bond strength has the most significant impact on cohesive strength, whereas the friction coefficient exhibits a closer relationship with the internal friction angle; the initial Young’s modulus is negatively correlated with the stiffness ratio, while other parameters having negligible impact. In the variation relationship related to Poisson’s ratio, the stiffness ratio has a more pronounced influence than the others. These research findings can not only provide a reference for the calibration of mesoscopic parameters in particle flow simulations of graded aggregate but also offer a basis for the research on mechanical properties of graded aggregates as road base fill.