Exposure of denture base acrylic resins to the oral environment and storage media for extended periods of time results in sorption of saliva or water, leading to a reduction in physical properties and thus clinical service life. The purpose of this in vitro study was to assess the sorption and solubility of high-impact heat-polymerised denture base acrylic resin (HI PMMA) impregnated with zirconia nanoparticles after being stored for 180 days in distilled water (DW) and artificial saliva (AS). The specimens were divided into six groups for each storage medium, according to the concentration of zirconia nanoparticles (0, 1.5, 3.0, 5.0, 7.0, and 10.0 wt.%). Data were statistically analysed for sorption and solubility using one-way and two-way ANOVA statistical tests. Sorption in DW and AS for all groups containing zirconia showed sorption values lower than the control group at 90 days, though not significantly different (p > 0.05) compared to the control group. For both the DW and AS groups, the lowest solubility value was measured in the group containing 3 wt.% zirconia, however, there was no significant difference compared to the control group except when observing 10 wt.% zirconia in AS, which showed a significantly higher solubility (p < 0.05). High-impact PMMA, impregnated with low concentrations of ZrO2, showed the lowest sorption and solubility in both media, but was not significantly different compared to pure HI PMMA.