Fatigue loading causes accumulation of damage that may lead to the initiation of a macrocrack and result in a catastrophic failure of bone. The objective of this study was to examine the influence of fatigue damage on crack growth parameters in bovine cortical bone. Nineteen rectangular beam specimens (4 × 4 × 48 mm) were machined from bovine tibiae. The long axis of the beams was aligned with the long axis of bones. Using a four-point bending fatigue setup, ten specimens were fatigue-damaged to different levels as indicated by stiffness loss. A through-thickness notch was machined at the center of each damaged and undamaged beam. The notched specimens were then monotonically loaded beyond failure using a three-point bending protocol. Critical stress intensity factor, K_I, and work to critical load, W_Q, were significantly lower in the damaged group than in the undamaged group (p < 0.03). When the undamaged specimens were assigned a percent stiffness loss of zero and pooled with the damaged group, significant negative correlations of percent stiffness loss with K_I (R = 0.58, p < 0.01), W_Q (R = 0.54, p < 0.02), maximum load, P_max (R = 0.59, p < 0.008), deflection at maximum load, Δ_max (R = 0.48, p < 0.04), structural stiffness, S_max (R = 0.53, p < 0.02), W_max (R = 0.55, p < 0.02), and load at 1.4 mm deflection (a value beyond failure but without complete fracture), P_1.4 (R = 0.47, p < 0.05), were found. Post hoc analysis revealed that the average load-deflection curve from the damaged group was transformable into that from the undamaged group through a special shift on the load-deflection plane. Fatigue damage reduces bone stiffness and resistance to crack initiation, maximum load-carrying capacity, and deflection before and after failure in cortical bone. The data suggest there is a single rule that governs the overall effect of fatigue damage on the fracture behavior of cortical bone.