(1) Background: Due to advantages such as avoidance of chipping, pulp-friendly tooth preparation and cost reduction, zirconia is increasingly being used monolithically without veneering. Nevertheless, to enable good aesthetics, various multilayer systems have been developed. The aim of this study was to investigate the impact of different zirconia multilayer strategies and yttria levels on fracture load, fracture pattern, stress distribution and surface roughness. (2) Methods: Monolithic three-unit anterior FDPs were made from three different color-gradient zirconia multilayer materials with different yttria levels corresponding to varying strength and degrees of translucency grades (Katana HTML, STML, UTML, Kuraray) and one strength-gradient zirconia multilayer material (Katana YML, Kuraray) and artificially aged in a chewing simulator (1.2 × 10⁶ load cycles, 50 N, 2 × 3000 thermocycles, 5–55 °C). Analyses of fracture load, fracture pattern, fracture surfaces, stress distribution and roughness were performed after the fracture load test. Shapiro–Wilk, Kruskal–Wallis, Mann–Whitney U-tests and one-way ANOVA were used (p < 0.05). (3) Results: Fracture loads of the high strength color-gradient material HTML and the strength-gradient material YML were comparable after 5 years of aging (p = 0.645). Increasing yttria levels resulted in a decrease in fracture resistance of 42–57% (p < 0.05). Surface roughness of different zirconia generations is comparable after polishing and aging. (4) Conclusions: Color-gradient multilayer zirconia materials and new strength-gradient zirconia materials with similar yttria levels in the basal layers show comparable mechanical properties and are suitable for anterior FDPs.