Hybrid ceramics exhibit low wear on antagonist tooth enamel, which may positively impact the oral rehabilitation of head-and-neck irradiated patients who experience alterations in tooth microstructure and wear resistance. This study aimed to evaluate the wear resistance of hybrid ceramics after gamma radiation exposure in contact with irradiated tooth enamel, as well as their mechanical and chemical properties. Notably, no previous studies focusing on the effects of radiation on hybrid ceramics were found in the literature. Vita Enamic discs and tooth fragments were subjected to daily doses of 2 Gy, totaling 0, 20, 40, 50, 60, and 70 Gy. The wear resistance of hybrid ceramics and a ceramic enamel analog (steatite) was tested against tooth enamel using a chewing simulation machine. Hybrid ceramic specimens underwent hardness, biaxial flexural strength, roughness, and FT-IR analyses. The data were analyzed using an ANOVA and Tukey's test (α = 0.05). Enamic exposed to 60 and 70 Gy exhibited higher wear and caused less tooth enamel loss compared to steatite. The mechanical and chemical properties remained unchanged after irradiation. The roughness decreased across all groups after a chewing simulation but was not affected by irradiation. In conclusion, ionizing radiation did not alter the material's properties but increased its wear.