The accurate assessment of running safety during earthquakes is of significant importance for ensuring the safety of railway lines. Currently, assessment methods based on a single index suffer from issues such as misjudgment of operational safety and difficulty in evaluating operational margin, making them unsuitable for assessing train safety during earthquakes. Therefore, in order to propose an effective evaluation method for the running safety of trains during earthquakes, this study employs three indexes, namely lateral displacement of the wheel–rail contact point, wheel unloading rate, and wheel lift, to describe the lateral and vertical contact states between the wheel and rail. The corresponding evolution characteristics of the wheel–rail contact states are determined, and the derailment forms under different frequency components of seismic motion are identified through dynamic numerical simulations of the train–track coupled system under sine excitation. The variations in the wheel–rail contact states during the transition from a safe state to the critical state of derailment are analyzed, thereby constructing the evolutionary path of train derailment and seismic derailment risk domain. Lastly, the wheel–rail contact and derailment states under seismic conditions are analyzed, thus verifying the effectiveness of the evaluation method for assessing running safety under earthquakes proposed in this study. The results indicate that the assessment method based on the derailment risk domain accurately and comprehensively reflects the wheel–rail contact states under seismic conditions. It successfully determines the forms of train derailment, the risk levels of derailment, and the evolutionary paths of derailment risk.