Statement of Problem: Polymethyl methacrylate (PMMA) denture resins commonly fracture as a result of the denture being dropped or when in use due to heavy occlusal forces. Purpose: To investigate the effects of E-glass fibre, ZrO2 and TiO2 nanoparticles at different concentrations on the fracture toughness and impact strength of PMMA denture base. Materials and Methods: To evaluate fracture toughness (dimensions: 40 × 8 × 4 mm3; n = 10/group) and impact strength (dimensions: 80 × 10 × 4 mm3; n = 12/group), 286 rectangular tested specimens were prepared and divided into four groups. Group C consisted of the PMMA specimens without any filler (control group), while the specimens in the remaining three groups varied according to the concentration of three filler materials by weight of PMMA resin: 1.5%, 3%, 5%, and 7%. Three-point bending and Charpy impact tests were conducted to measure the fracture toughness and impact strength respectively. Scanning Electron Microscope (SEM) was utilised to examine the fractured surfaces of the specimens after the fracture toughness test. One-way analysis of variance (ANOVA) followed by Tukey post-hoc tests were employed to analyse the results at a p ≤ 0.05 significance level. Results: Fracture toughness of groups with 1.5 and 3 wt.% ZrO2, 1.5 wt.% TiO2, and all E-glass fibre concentrations were significantly higher (p < 0.05) than the control group. The samples reinforced with 3 wt.% ZrO2 exhibited the highest fracture toughness. Those reinforced with a 3 wt.%, 5 wt.%, and 7 wt.% of E-glass fibres had a significantly (p < 0.05) higher impact strength than the specimens in the control group. The heat-cured PMMA modified with either ZrO2 or TiO2 nanoparticles did not exhibit a statistically significant difference in impact strength (p > 0.05) in comparison to the control group. Conclusions: 1.5 wt.%, 3 wt.% of ZrO2; 1.5 wt.% ratios of TiO2; and 1.5 wt.%, 3 wt.%, 5 wt.%, and 7 wt.% of E-glass fibre can effectively enhance the fracture toughness of PMMA. The inclusion of E-glass fibres does significantly improve impact strength, while ZrO2 or TiO2 nanoparticles did not.