Background and Objectives: To evaluate in vitro the fracture resistance and fracture type of computer-aided design and computer-aided manufacturing (CAD-CAM) materials. Materials and Methods: Discs were fabricated (10 × 1.5 mm) from four test groups ( N = 80; N = 20 per group): lithium disilicate (LDS) group (control group): IPS e.max CAD®; zirconium-reinforced lithium silicate (ZRLS) group: VITA SUPRINITY®; polymer-infiltrated ceramic networks (PICN) group: VITA ENAMIC®; resin nanoceramics (RNC) group: LAVA™ ULTIMATE. Each disc was cemented (following the manufacturers’ instructions) onto previously prepared molar dentin. Samples underwent until fracture using a Shimadzu® test machine. The stress suffered by each material was calculated with the Hertzian model, and its behavior was analyzed using the Weibull modulus. Data were analyzed with ANOVA parametric statistical tests. Results: The LDS group obtained higher fracture resistance (4588.6 MPa), followed by the ZRLS group (4476.3 MPa) and PICN group (4014.2 MPa) without statistically significant differences ( p < 0.05). Hybrid materials presented lower strength than ceramic materials, the RNC group obtaining the lowest values (3110 MPa) with significant difference ( p < 0.001). Groups PICN and RNC showed greater occlusal wear on the restoration surface prior to star-shaped fracture on the surface, while other materials presented radial fracture patterns. Conclusion: The strength of CAD-CAM materials depended on their composition, lithium disilicate being stronger than hybrid materials.