This paper presents experimental and theoretical analyses of the second harmonic generation due to non-linear interaction of Lamb waves with a fatigue crack. Three-dimensional (3D) finite element (FE) simulations and experimental studies are carried out to provide physical insight into the mechanism of second harmonic generation. The results demonstrate that the 3D FE simulations can provide a reasonable prediction on the second harmonic generated due to the contact nonlinearity at the fatigue crack. The effect of the wave modes on the second harmonic generation is also investigated in detail. It is found that the magnitude of the second harmonic induced by the interaction of the fundamental symmetric mode (S-0) of Lamb wave with the fatigue crack is much higher than that by the fundamental anti-symmetric mode (A(0)) of Lamb wave. In addition, a series of parametric studies using 3D FE simulations are conducted to investigate the effect of the fatigue crack length to incident wave wavelength ratio, and the influence of the excitation frequency on the second harmonic generation. The outcomes show that the magnitude and directivity pattern of the generated second harmonic depend on the fatigue crack length to incident wave wavelength ratio as well as the ratio of So to A(0) incident Lamb wave amplitude. In summary, the findings of this study can further advance the use of second harmonic generation in damage detection. (C) 2017 Elsevier Ltd. All rights reserved.