Long-span railway bridges crossing active faults are more vulnerable owing to the joint combination of pulse ground motions and surface dislocation. To study the dynamic effects resulting from the coupling of long-span railway suspension bridges crossing strike–slip fault and trains, a nonlinear model in which wheel–rail contact was established based on Hertz’s nonlinear theory and Kalker creep theory. To generate the ground motions across strike–slip fault, an artificial synthetic method, which considers both the fling-step effect with a single pulse and the directivity effect with multiple pulses, is employed. The effects of fault-crossing angles (FCAs) and permanent ground rupture displacements (PGRDs) are systematically investigated based on wheel–rail dynamic (derailment coefficient, lateral wheel–rail force, and wheel–load reduction rate). Conclusions are drawn and can be applied in the practical seismic design and train running safety assessment of long-span railway suspension bridges crossing strike–slip fault.