The purpose of this study was to evaluate and compare the changes in the various mechanical properties of hybrid and conventional CAD/CAM materials after accelerated aging using hydrothermal processes.Five kinds of hybrid and ceramic CAD/CAM blocks were selected. A total of 225 specimens were prepared with highly polished surfaces, in the form of round discs (diameter 12 mm, thickness 1.2 mm), and were divided into three groups (the control group, thermal cycling group, and autoclave group [n = 15, each]). The nanoindentation hardness and Young's modulus (nanoindenter), biaxial flexural strength (ball-on-ring test system), surface roughness (atomic force microscopy), surface texture (scanning electron microscopy (SEM)), and elemental concentrations (energy dispersive spectroscopy) were evaluated. The Kruskal–Wallis test and Mann–Whitney U test were used to determine statistical significance (P < 0.05).The nanoindentation hardness and Young's modulus of the hybrid CAD/CAM materials were lower than those of ceramic materials, and they decreased after autoclave treatment. Among the hybrid CAD/CAM materials, Vita Enamic alone showed no significant difference in the Young's modulus after autoclave treatment; it also exhibited the highest nanoindentation hardness and modulus. There were significant changes in the biaxial flexural strength of hybrid CAD/CAM materials after aging. However, there was no change in the biaxial flexural strength of ceramic materials. The surface roughness of all materials, except CeraSmart, changed after aging. The SEM observations indicated a loss of filler particles in Lava Ultimate and morphological changes in IPS e.max ZirCAD, after aging.The ceramic CAD/CAM materials are superior to hybrid CAD/CAM materials in terms of the mechanical properties. The accelerated aging procedure induced changes in the mechanical properties of some hybrid CAD/CAM materials. Therefore, when using hybrid CAD/CAM materials, it is important to understand the behaviors of the various properties of each material as time progresses, and long-term follow up is necessary.