Owing to the extensive worldwide generation of solid wastes, such as rubber tires, and the resulting adverse environmental impacts, the incorporation of these waste materials in construction projects has become a widespread aim. However, concerns have arisen regarding the effects of rubber waste on the mechanical properties of Portland cement concrete (PCC) mixes. Thus, this study investigates the effects of replacing natural coarse aggregates with tire-derived aggregates (TDA). In PCC mixes, natural aggregates were replaced by 0, 10, 20, 40, 60, 80, and 100% TDA by volume, and the properties of these specimens were tested in the laboratory. The results obtained were then used as inputs for the KENPAVE software, to evaluate induced stresses, deflections, and cracking indices in rigid pavement slabs, with eleven different thicknesses, ranging from 200 to 300 mm in 10 mm increments. Stresses under different loading conditions decreased as PCC slab thickness and TDA content increased. Increased deflection and cracking indices resulting from adding TDA could be counteracted by increasing the PCC slab thickness by 10 mm. Moreover, environmental impacts and cost analyses were examined via PaLATE 2.0, which showed that the use of TDA could reduce energy consumption, harmful emissions, and material costs. Overall, this study indicates that the use of TDA in PCC mixes has benefits that can make it a good candidate for sustainable, ecofriendly rigid pavement construction projects.