Understanding of fracture mechanics of the human knee structures within total knee replacement (TKR) allows a better decision support for bone fracture prevention. Numerous studies addressed these complex injuries involving the femur bones but the full macro-crack propagation from crack initiation to final failure and age-related effects on the tibia bone were not extensively studied. The present study aimed to develop a patient-specific model of the human tibia bone and the associated TKR implant, to study fatigue and fracture behaviors under physiological and pathological (i.e., age-related effect) conditions. Computed tomography (CT) data were used to develop a patient-specific computational model of the human tibia bone (cortical and cancellous) and associated implants. First, segmentation and 3D-reconstruction of the geometrical models of the tibia and implant were performed. Then, meshes were generated. The locations of crack initiation were identified using the clinical observation and the fatigue crack initiation model. Then, the propagation of the crack in the bone until final failure was investigated using the eXtended finite element method (X-FEM). Finally, the obtained outcomes were analyzed and evaluated to investigate the age-effects on the crack propagation behaviors of the bone. For fatigue crack initiation analysis, the stress amplitude–life S–N curve witnessed a decrease with increasing age. The maximal stress concentration caused by cyclic loading resulted in the weakening of the tibia bone under TKR. For fatigue crack propagation analysis, regarding simulation with the implant, the stress intensity factorand the energy release rate tended to decrease, as compared to the tibia model without the implant, from 0.152.5 to 0.111.9 (MPa) and from 10240 to 5133 (J), respectively. This led to the drop in crack propagation speed. This study provided, for the first time, a detailed view on the full crack path from crack initiation to final failure of the tibia bone within the TKR implant. The obtained outcomes also suggested that age (i.e., bone strength) also plays an important role in tibia crack and bone fracture. In perspective, patient-specific bone properties and dynamic loadings (e.g., during walking or running) are incorporated to provide objective and quantitative indicators for crack and fracture prevention, during daily activities.