Waste materials may be used as raw materials for interlocking masonry products in order to contribute to sustainable development and environmental protection. Rubberized concrete Interlocking Brick (RCIB) was developed by volumetric replacement of 56 of the ordinary Portland cement with fly ash and 20 of the sand with crumb rubber (CR) to reduce the production cost of conventional concrete bricks (CCB) and restrict the depletion of natural resources and contributing to solving the environmental problems associated with the accumulation of scrap tires in landfills. The mechanical and sustainability evaluation of masonry prism made of the developed brick is the aim of this research. Consequently, compressive strength, failure mechanism, stress-strain behaviour, and energy absorption of grouted and ungrouted prisms made of RCIB were measured experimentally under axial compression load. The thermal resistance, fuel consumption, CO2 emission, and cost analysis of RCIBs were estimated. The findings reveal that grout had a significant impact on the compressive strength of rubberized concrete interlocking masonry prisms where the compressive strength of grouted and ungrouted prisms was 10.99 MPa and 5.83 MPa, respectively. Web splitting and vertical cracks were the common failure modes observed in both prisms. Moreover, the rubberized concrete interlocking masonry prisms revealed greater energy absorption as well as a gradual and ductile failure mechanism. The RCIB exhibited higher thermal resistance than CCB (increased from 0.106 to 0.171 m2 K/W) which could contribute to a 62 reduction in annual fuel consumption and CO2 emission. Further, more than 25 of the material cost could be saved. © 2022 The Author(s).