This paper presents the assessment of fatigue crack growth rate for dual-phase steel under spectrum loading based on entropy generation. According to the second law of thermodynamics, fatigue crack growth is related to entropy gain because of its irreversibility. In this work, the temperature evolution and crack length were simultaneously measured during fatigue crack growth tests until failure to ensure the validity of the assessment. Results indicated a significant correlation between fatigue crack growth rate and entropy. This relationship is the basis in developing a model that can determine the characteristics of fatigue crack growth rates, particularly under spectrum loading. Predictive results showed that the proposed model can accurately predict the fatigue crack growth rate under spectrum loading in all cases. The root mean square error in all cases is 10−7 m/cycle. In conclusion, entropy generation can accurately predict the fatigue crack growth rate of dual-phase steels under spectrum loading.