To evaluate the failure-load and survival-rate of screw-retained monolithic and bi-layered crowns bonded to titanium-bases before and after mouth-motion fatigue, 72 titanium-implants (SICvantage-max, SIC-invent-AG) were restored with three groups (n = 24) of screw-retained CAD/CAM implant-supported-single-crowns (ISSC) bonded to titanium-bases: porcelain-fused-to-metal (PFM-control), porcelain-fused-to-zirconia (PFZ-test) and monolithic LDS (LDS-test). Half of the specimens (n = 12/group) were subjected to fatigue in a chewing-simulator (1.2 million cycles, 198 N, 1.67 Hz, thermocycling 5–55 °C). All samples were exposed to single-load-to-failure without (PFM0, PFZ0, LDS0) or with fatigue (PFM1, PFZ1, LDS1). Comparisons were statistically analyzed with t-tests and regression-models and corrected for multiple-testing using the Student–Neuman–Keuls method. All PFM and LDS crowns survived fatigue exposure, whereas 16.7% of PFZ showed chipping failures. The mean failure-loads (±SD) were: PFM0: 2633 ± 389 N, PFM1: 2349 ± 578 N, PFZ0: 2152 ± 572 N, PFZ1: 1686 ± 691 N, LDS0: 2981 ± 798 N, LDS1: 2722 ± 497 N. Fatigue did not influence load to failure of any group. PFZ ISSC showed significantly lower failure-loads than monolithic-LDS regardless of artificial aging (p < 0.05). PFM ISSC showed significantly higher failure loads after fatigue than PFZ (p = 0.032). All ISSC failed in a range above physiological chewing forces. Premature chipping fractures might occur in PFZ ISSC. Monolithic-LDS ISSC showed high reliability as an all-ceramic material for screw-retained posterior hybrid-abutment-crowns.