The derailment of a high‐speed train is a complex and uncertain dynamic process, especially under running conditions where the derailment index lacks comprehensive experimental validation. This research focuses on elucidating the mechanism of an earthquake‐induced train derailment and validating the structural response‐based spectrum intensity derailment index. To achieve this, a multi‐array shaking table system was utilized to test the safety of a running train and to physically replicate train derailment process under severe earthquake impact. We investigated the vibration characteristics and derailment progression of trains operating at different speeds, exposed to earthquakes of varying frequencies and intensities. In stationary derailments, significant wheelset lift was observed due to lateral rolling vibrations. However, in running test cases, there was no separation between the wheels and rails. Instead, the wheels underwent a long period of climbing and descending on the rails, similar to damped single‐degree‐of‐freedom oscillations. As the wheel climbed the rail and reached a critical potential energy point, the wheel flange of the wheel could potentially fall due to gravity or come off the rail due to external disturbances. The critical potential energy could be represented by the spectrum intensity threshold, and the prediction results aligned well with the derailment test results for both stationary and running trains. Furthermore, the method of determining train derailment based on structural responses was consistent with the test results. The spectrum intensity index shows strong positive correlations with other wheel‐force‐related indicators, albeit adopting a conservative perspective, reinforcing its efficacy in assessing train safety.