<p>Opportunities to manufacture sustainable masonry units with less of an impact on the environment and sufficient durability under demanding service circumstances have been made possible by the growing use of industrial by-products in construction. Nevertheless, there is still a lack of knowledge regarding the long-term chemical durability of composite interlocking bricks that incorporate various waste materials under various exposure conditions. The mechanical performance and chemical durability of composite interlocking bricks made from fly ash (FA), manufactured sand (MS), lime, gypsum, crushed rubber (CR), and granite waste powder (GWP) as partial substitutes for traditional ingredients are assessed in this study. Hydraulic compression molding was used to create two brick sizes, which were assessed using compressive strength testing, chemical exposure to 5% sodium chloride (NaCl), 5% sodium sulfate (Na₂SO₄), and natural seawater for up to 120 days, as well as scanning electron microscopy (SEM) and energy-dispersive X-ray spectroscopy (EDS) of the prepared powder mixture. While combinations with 20–30% GWP showed better resistance to sulfate and chloride intrusion, the optimized mixture with 30% GWP had the best compressive strength. The results show that the mechanical performance and chemical durability of composite interlocking bricks are greatly improved by the proper use of industrial waste materials.</p>