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The cement industry is one of the largest contributors to global carbon dioxide emissions, prompting a growing demand for sustainable alternatives. This study investigates the potential of wheat straw ash (WSA), an abundant agricultural waste, as a partial replacement for cement in concrete. Utilizing Response Surface Methodology (RSM), the research aims to optimize key mix parameters to achieve the best balance between mechanical performance and environmental benefits. A series of concrete mixes were prepared with varying WSA replacement levels (0%–20%) and water-to-binder ratios. Experimental responses, including compressive strength and workability, were evaluated and statistically analyzed using a Central Composite Design (CCD) framework. The results demonstrate that an optimal WSA content can significantly enhance the sustainability of concrete with minimal compromise on strength and durability. This optimization approach offers a promising pathway for incorporating agricultural waste into construction materials, contributing to circular economy goals and reduction of greenhouse gas emissions.