Ceramic restorations, whether monolithic (single layer) or porcelain-veneered, often chip and fracture from repeated occlusal loading. Occlusion involves the opposing tooth sliding along the cuspal incline surface with an applied biting force (off-axis loading). We hypothesized that off-axis contact-load-slide-liftoff fatigue, as compared with normal axial fatigue loading, produces different fracture modes and fatigue lifespans of layered ceramics. Monolithic glass plates were epoxy-bonded to polycarbonate substrates as a transparent model for an all-ceramic crown on dentin. Off-axis and axial (control) cyclic loading was applied through a hard sphere in water, with a mouth-motion machine. The off-axis loading is more deleterious for contact-induced occlusal surface fracture, but less harmful for flexure-induced cementation surface fracture of brittle layers than the axial loading. This is because of the tangential load component associated with the off-axis loading. Clinical relevance is discussed.