Microdamage accumulation has been identified as a major conduit for bone tissues to absorb fracture energy. Due to the poor understanding of its underlying mechanism, however, an adequate constitutive relationship between damage accumulation and the mechanical behavior of bone has not yet been established. In this study, the constitutive relationship between the damage accumulation induced by overload and the evolution of mechanical properties of bone with incremental deformation was established based on the experimental results obtained from a novel progressive loading protocol developed in our laboratory. First, a decayed exponential model was proposed to capture the damage accumulation (modulus loss) with increase in applied strain. Next, a power law function was proposed to represent the progression of plastic deformation with damage accumulation. Finally, a linear combination of the Kohlrausch–Williams–Watts (KWW) and the Debye functions was used to depict the viscoelastic behavior of bone associated with damage accumulation. The results of this study may help in developing a constitutive model for predicting the mechanical behavior of cortical bone tissues.