The fracture resistance of computer-aided designing and computer-aided manufacturing CAD/CAM fabricated implant-supported cantilever zirconia frameworks (ISCZFs) is affected by the size/dimension and the micro cracks produced from diamond burs during the milling process. The present in vitro study investigated the fracture load for different cross-sectional dimensions of connector sites of implant-supported cantilever zirconia frameworks (ISCZFs) with different cantilever lengths (load point). A total of 48 ISCZFs (Cercon, Degudent; Dentsply, Deutschland, Germany) were fabricated by CAD/CAM and divided into four groups based on cantilever length and reinforcement of distal-abutment: Group A: 9 mm cantilever; Group B: 9 mm cantilever with reinforced distal-abutment; Group C: 12 mm cantilever; Group D: 12 mm cantilever with reinforced distal-abutment (n = 12). The ISCZFs were loaded using a universal testing machine for recording the fracture load. Descriptive statistics, ANOVA, and Tukey’s test were used for the statistical analysis (p < 0.05). Significant variations were found between the fracture loads of the four ISCZFs (p = 0.000); Group-C and B were found with the weakest and the strongest distal cantilever frameworks with fracture load of 670.39 ± 130.96 N and 1137.86 ± 127.85 N, respectively. The mean difference of the fracture load between groups A (810.49 + 137.579 N) and B (1137.86 ± 127.85 N) and between C (670.39 ± 130.96 N) and D (914.58 + 149.635 N) was statistically significant (p = 0.000). Significant variations in the fracture load between the ISCZFs with different cantilever lengths and thicknesses of the distal abutments were found. Increasing the thickness of the distal abutment only by 0.5 mm reinforces the distal abutments by significantly increasing the fracture load of the ISCZFs. Therefore, an increase in the thickness of the distal abutments is recommended in patients seeking implant-supported distal cantilever fixed prostheses.