This research analyzes the very-high-cycle-fatigue behavior of TC4 titanium alloy through fatigue tests at R = −1, −0.3, and 0.1. The results show that the S-N curves are all bilinear and exhibit three failure modes as surface slip failure, surface cleavage failure and interior cleavage failure. Transmission electron microscopy analysis reveals the dislocation structure in interior cleavage failure and suggests that the deformation mechanism of faceting cracking involves both anti-phase boundary shearing and stacking fault shearing mechanisms. It concludes that interior failure results from cleavage fracture of α grains due to dislocation slip. Based on the stress intensity factor of the maximum defect, a slip-cleavage competitive failure model was developed by considering factors such as control volume, defect size, external loading, and grain content, with good predictive results. Additionally, on the basis of the failure mechanism and crack propagation rate model, considering the coupled effects of crack tip blunting, stress ratio, Vickers hardness, and material fracture toughness on crack propagation, the crack propagation life prediction model is constructed. The life prediction model is further modified to be more conservative and accurate in predicting life by consideration the maximum defect size, providing important theoretical support and practical guidance for engineering applications.