Extrusion is an efficient hot working process to aluminum production and AISI H13 (4Cr5MoSiV1) as the main material of extrusion tool suffers from fatigue and creep damage due to its extreme working condition. A new mean plastic strain life prediction has been proposed based on the energy method. In addition, statistical analysis is also taken into consideration to complement this physic-based model due to other unmeasured and unknown exogenous influences. To validate the model, a series of AISI H13 fatigue and fatigue–creep tests were conducted at 500 °C close to the practical aluminum extrusion process. The strain-controlled tests were used for obtaining the parameters, while the stress-controlled tests were utilized for validating the proposed model. It shows that the model predictions were in good agreement with the experimental results.