Purpose: The mechanical strength of polymethyl methacrylate (PMMA) remains far from ideal for maintaining the longevity of denture. The purpose of this study was to evaluate the effect of Zirconium oxide (ZrO₂) nanofillers powder with different concentration (1.5%, 3%, 5% and 7%) on the flexural strength, fracture toughness, and hardness of heat-polymerized acrylic resin. Materials and methods: Zirconium oxide powders with different concentrations (1.5%, 3%, 5% and 7%) were incorporated into heat-cure acrylic resin (PMMA) and processed with optimal condition (2.5:1 Powder/monomer ratio, conventional packing method and water bath curing for 2 hours at 95^。C) to fabricate test specimens of PMMA of dimensions (50 × 30 × 30 mm) for the flexural strength, fracture toughness, and (50 × 30 × 30 mm) were fabricated for measuring hardness. PMMA without additives was prepared as a test control. Three types of mechanical tests; flexural strength, fracture toughness and hardness were carried out on the samples. The recorded values of flexural strength in (MPa), fracture toughness in (MPa.m^1/2), and hardness (VHN) were collected, tabulated and statistically analyzed. One way analysis of variance (ANOVA) and Tukey’s tests were used for testing the significance between the means of tested groups which are statistically significant when the P value ≤ 0.05. Results: Addition of Zirconium oxide nanofillers to PMMA significantly increased the flexural strength, fracture toughness and hardness. Conclusion: These results indicate that Zirconium oxide nanofillers added to PMMA has a potential as a reliable denture base material with increased flexural strength, fracture toughness, and hardness. According to the results of the present study, the best mechanical properties were achieved by adding 7%wt ZrO₂ concentration.