Due to the complex structures and severe working conditions, including the erosion of high-temperature gas and alternating combustion pressure, the thermal–mechanical fatigue is more likely to occur on the loading surface, which will also have serious impacts on the reliability of marine diesel engine. Herein, based on the three-dimensional fluid–solid coupling analysis, a highly effective four-zone heat transfer model is proposed for analyzing the rules of fatigue life of a new-type high power density diesel engine cylinder head, which can greatly simplify the calculation process of thermal fluid–solid coupling and improve the analysis efficiency by 95%. The accuracy of the model is verified by the temperature field test (with the maximum error of 5.6%) and mechanical fatigue test (with the maximum error of 4.1%). The influence law of operating conditions such as in-cylinder pressure and temperature on high cycle fatigue (HCF) and low cycle fatigue (LCF) life is analyzed. Therefore, the generalized Eying model is obtained, which can establish a direct relationship among the cylinder head fatigue life, average gas temperature as well as maximum combustion pressure, potentially providing the reliability evaluation and optimization design for the diesel engine.