This research article aims at investigating the novel use of Graphene Oxide (GO) as a nano-reinforcement in cement mortar made entirely with manufactured sand (M-sand), focusing on both mechanical performance and chemical durability. GO was added in dosages ranging from 0.00% to 0.10% by weight of cement, increasing in 0.02% increments. The study uniquely combines nano-modification with 100% M-sand use, targeting sustainable and high-performance construction materials. Compressive strength testing showed clear improvements with GO incorporation. The optimal dosage was 0.06%, yie lding 36.05 N/mm² at 7 days, 42.21 N/mm² at 28 days, and 58.13 N/mm² at 56 days. Higher dosages led to a slight decline, likely due to GO agglomeration. Durability was tested by immersing 56-day cured specimens for 28 days in 2% H₂SO₄, 5% MgSO₄, and 3% NaCl solutions. The 0.06% GO mix retained 64.5% strength under acid attack, 70.4% under sulphate, and 86.9% (50.5 N/mm²) under chloride exposure—significantly outperforming the control. Weight loss measurements mirrored strength trends. GO-modified specimens experienced much less degradation, with up to 10.8% lower mass loss under acid attack and similar benefits under sulphate and chloride exposure. In conclusion, GO at 0.06% enhances both strength and chemical durability of 100% M-sand cement mortar, marking it as a promising nano-additive for eco-friendly, long-lasting cementitious systems in aggressive environments.