The rehabilitation of free-end situations is a frequent indication in prosthetic dentistry. Cantilever fixed dental prostheses (cFDPs) made of 1st and 2nd generation zirconia are one treatment option. Due to a unique gradient technology, combinations of different zirconium dioxide generations are thus feasible in one restoration. However, data about these materials are rare. The purpose of this study was therefore to investigate the fracture resistance and fracture modes of tooth-supported cFDPs fabricated from different zirconia materials (gradient technology) and different framework thicknesses. A total of 40 cFDPs were fabricated using the CAD/CAM approach and belonged to five test groups. The different groups differed in the yttria content, the proportion of the tetragonal/cubic phases, or in wall thickness (0.7 mm or 1 mm). After completion, the cFDPs were subjected to thermal cycling and chewing simulation (1.2 × 106 load cycles, 108 N load). Afterwards, cFDPs were statically loaded until fracture in a universal testing machine. A non-parametric ANOVA was compiled to determine the possible effects of group membership on fracture resistance. In addition, post-hoc Tukey tests were used for bivariate comparisons. The mean fracture loads under axial load application ranged from 288 to 577 N. ANOVA detected a significant impact of the used material on the fracture resistances (p < 0.001). Therefore, the use of cFDPs fabricated by gradient technology zirconia may not be unreservedly recommended for clinical use, whereas cFPDs made from 3Y-TZP exhibit fracture resistance above possible masticatory loads in the posterior region.