Buildings account for a significant portion of global energy consumption and greenhouse gas emissions, making the development of energy-efficient and sustainable construction materials a pressing necessity. Fly ash-based concrete (FA-concrete) has emerged as a promising alternative to traditional cement-based materials due to its potential to improve thermal performance, reduce energy demands, and lower environmental impacts. This study presents a comparative analysis of the thermal performance and energy efficiency of buildings constructed using fly ash-based concrete versus traditional cement-based masonry. To evaluate the energy efficiency of the developed FA-based concrete in comparison with conventional materials, building simulation models were created using the TRNSYS software. Experimental data on the thermophysical properties of the FA-concrete and conventional concrete were incorporated into the simulation model. The simulations were conducted throughout the year under the climatic conditions of Oujda, Morocco, a region characterized by extreme seasonal temperature fluctuations. Results indicate that, in the absence of heating or cooling systems, buildings constructed with FA-based mortar maintained temperatures approximately 1 °C cooler in the summer and 0.5 °C warmer in the winter compared to those made with conventional concrete. Moreover, when heating and cooling systems were employed, buildings using FA-based concrete showed a 15.5% reduction in energy consumption, underscoring the material’s energy-saving potential. In addition to environmental and ecological advantages (through waste recycling), these findings highlight the significant economic benefits of using industrial waste products—such as fly ash—in construction. Overall, the results emphasize the potential of sustainable building materials in reducing both the carbon footprint and energy consumption in the construction sector.