In recent years, due to the reduction in available natural resources, the attention of many researchers has been focused on the reuse of recycled materials and industrial waste in common engineering applications. This paper discusses the feasibility of using seven different materials as alternative fillers instead of ordinary Portland cement (OPC) in road pavement base layers: namely rice husk ash (RHA), brick dust (BD), marble dust (MD), stone dust (SD), fly ash (FA), limestone dust (LD), and silica fume (SF). To exclusively evaluate the effect that selected fillers had on the mechanical performance of asphalt mixtures, we carried out Marshall, indirect tensile strength, moisture susceptibility, and Cantabro abrasion loss tests on specimens in which only the filler type and its percentage varied while keeping constant all the remaining design parameters. Experimental findings showed that all mixtures, except those prepared with 4% RHA or MD, met the requirements of Indian standards with respect to air voids, Marshall stability and quotient. LD and SF mixtures provided slightly better mechanical strength and durability than OPC ones, proving they can be successfully recycled as filler in asphalt mixtures. Furthermore, a Machine Learning methodology based on laboratory results was developed. A decision tree Categorical Boosting approach allowed the main mechanical properties of the investigated mixtures to be predicted on the basis of the main compositional variables, with a mean Pearson correlation and a mean coefficient of determination equal to 0.9724 and 0.9374, respectively.