A practical method for predicting fatigue life of the main spar with wrinkle defects in a wind turbine blade is presented in this paper. First, the effect of different wrinkle geometry on stiffness in a composite laminate is quantified. Then, the model of intrinsic dissipated energy is proposed to determine the fatigue limit rapidly. A fatigue life prediction model containing unknown parameters is developed by introducing intrinsic dissipated energy to characterize stiffness degradation of the main spar laminate with wrinkle defects. The specimens with different wrinkle geometry are subjected to fatigue tests, monitored with an infrared thermography system to obtain experimental data. After determining the unknown parameters of the developed model, the S‐N curves of specimens are evaluated in a relatively short time. The predicted fatigue life is within the 95% confidence interval of lifetime obtained by the traditional tests, which suggests the developed model is accurate. This work is suitable for fatigue life prediction of main spar with different wrinkle defects.