Sultan Al-Ashraf Qaytbay mosque is viewed as one of the most beautiful achieved landmarks of late Egyptian Mamluk architecture. The mosque architectural design is considered exceptional for its refined extents and the subdued yet exquisite decorations. In this paper, Computational fluid dynamics (CFD) simulation joined with wind tunnel experiments are performed to investigate the airflow characteristics inside the mosque of Sultan Al-Ashraf Qaytbay due to natural ventilation brought about by window openings. Wind tunnel experiments are performed to provide the boundary conditions for the subsequent CFD simulations. The results of CFD simulation are contrasted with that of the wind tunnel experiments. The comparison demonstrates great agreement between the computational and experimental results, which confirms the legitimacy of the present computational procedure. Interesting outcomes and productive conclusions are inferred from the obtained results.