A nonlinear dynamic methodology is developed for detecting and estimating fatigue damage precursor in isotropic metal structures, prior to fatigue crack initiation, based on measurement of changes in the structure nonlinear response to harmonic base excitation. As an example, a damage precursor feature was extracted for cantilever beams by quantifying the reduction in the nonlinear stiffness because of localized microscopic material softening. The nonlinear dynamic analytical model parametrically tracks changes in the nonlinear structural stiffening as a function of the structural response and the loading cycles. Experimental results are obtained by exciting the base of cantilever beams at various amplitude levels. At high response amplitudes, the beams experience three competing simultaneous nonlinear dynamic mechanisms: (i) stiffening because of high response amplitude at the fundamental mode; (ii) softening because of inertial forces; and (iii) softening because of localized microscopic material damage caused by cyclic micro-plasticity. The third mechanism—a potential precursor to fatigue crack initiation in the structure—resulted in a cumulative softening because of early accumulation of cyclic fatigue damage and is the focus of this study. The loading intensity and the number of cycles influenced the relative contribution of these dynamic mechanisms. Nanoindentation studies near the beam clamped boundary were conducted to confirm the fatigue degradation in the local mechanical properties as a function of loading cycles. The proposed detection method is simple to implement and detects the presence of damage precursors but lacks the resolution to discern spatial distributions of the damage intensity. Based on prior knowledge of the structural dynamic characteristics of the beam and using the proposed methodology, damage level and stiffness reduction can be detected and estimated based on changes in the nonlinear structural response. The nonlinear stiffness term in the equation of motion is found to be very sensitive to the proposed fatigue damage precursor, making it an effective method for monitoring structural degradation prior to crack developments. The proposed methodology provides new insights and constitutes a significant step toward the development of new inspection techniques. Copyright © 2016 John Wiley & Sons, Ltd.