The random seismic analysis of long-span concrete filled steel-tube (CFST) arch bridge under multi-support excitations of three-dimensional orthogonal earthquake motion was performed. The precise finite element model of a 308 m span half-through CFST arch bridge was established. The seismic response of the arch bridge under one-dimensional P-wave, one-dimensional SH-wave, one-dimensional SV-wave and three-dimensional considering cross-power spectrum of multi-support earthquake excitations were numerically simulated by the method of the three-dimensional and multi-support stationary random seismic response, and the influence of three-dimensional earthquake motion, traveling-wave effect and partial coherence effect on arch rib were studied. The results show that the internal forces of arch rib may be greatly changed by considering the spatial variation of seismic motion. The influence of the traveling-wave effect of the earthquake motion on the internal forces of arch rib is greater than that of the partial coherence effect. The internal forces of arch rib under three-dimensional earthquake excitations are greater than that under one-dimensional excitation. The random seismic analysis under three-dimensional and multi-support earthquake excitations must be performed for the long-span CFST arch bridge otherwise the seismic design forces of the structure are likely to underestimate seriously.