This study aimed to measure the effect of storage environment on the hardness, surface roughness and wear ability of CAD/CAM resin-matrix ceramics. A total of 200 rectangular-shaped specimens were obtained by sectioning 5 CAD/CAM blocks; Crystal Ultra (CU), Vita Enamic (VE), Lava Ultimate (LU), Cerasmart (CS) and Vita blocks Mark II (MII). Microhardness and surface roughness were measured at baseline and after 7 days of immersion either in saliva or cola (n = 10). The wear ability of the CAD/CAM materials against steatite-ceramics antagonist was determined using a chewing simulator. The data were statistically analyzed using factorial ANOVA followed by post hoc Bonferroni multiple comparison tests (p < 0.05). The independent factors significantly influenced the microhardness and surface roughness (p < 0.05). The highest VHN was observed in MII at baseline (586.97 ± 13.95), while CU showed the lowest VHN after 7 days of immersion in cola (68.3 ± 1.89). On the contrary, the highest Ra was observed after 120,000 chewing cycles for the VE specimens (1.09 ± 0.43 µm) immersed in cola, while LU showed the lowest Ra at baseline (0.07 ± 0.01 µm). The highest % mass loss of the antagonist was observed with MII immersed in cola (1.801%), while CS demonstrated the lowest % mass loss of 0.004% and 0.007% in AS and cola, respectively. This study confirms that the surface properties of tested CAD/CAM materials are susceptible to degradation in an acidic environment except for hardness and wear of CS material.