© 2021 The Academy of Dental MaterialsObjective: To evaluate the fatigue failure load, number of cycles until failure and survival probability of partially (PSZ) and fully-stabilized (FSZ) polycrystalline zirconia disc shaped specimens with different thicknesses adhesively cemented onto foundations with distinct elastic moduli. Methods: Disc-shaped specimens (n = 15, Ø = 10 mm; thickness = 1.0 and 0.7 mm) of CAD/CAM PSZ and FSZ blocks were adhesively cemented onto discs with different foundations (Ø = 10 mm; thickness = 2.0 mm) made from epoxy resin, composite resin or Ni–Cr metallic alloy. The cemented assemblies were subjected to fatigue testing using a step-stress approach (600−2800 N; step-size of 100 N; 10,000 cycles per step; 20 Hz) and the data was submitted to specific statistical tests (α = 0.05). Fractography and finite element (FEA) analyzes were also performed. Results: PSZ and FSZ presented higher fatigue failure load, number of cycles until failure and survival probabilities when cemented onto metallic alloy. All PSZ specimens survived the fatigue test when cemented onto Ni–Cr alloy (100% probability of survival at 2800 N; 230,000 cycles). Regardless of the foundation type, PSZ had better fatigue behavior than FSZ. For thickness, thinner PSZ restorations underperformed when bonded to softer foundations, while FSZ groups and groups bonded to metallic foundations had no statistical difference. Significance: The foundation material strongly influences the fatigue performance of PSZ and FSZ restorations, which presented mechanical behavior improvements when bonded to a metallic foundation. PSZ restorations showed better fatigue behavior than FSZ, while the ceramic thickness only influenced PSZ restorations bonded to softer foundations.