Post-earthquake damages investigation in past and recent earthquakes has illustrated that the ground motion spatial variation plays an important role in the structural response of long span bridges. For the structural control of seismic-induced vibrations of cable-stayed bridges, it is extremely important to include the effects of the ground motion spatial variation in the analysis for design of an effective control system. The feasibility and efficiency of different vibration control strategies for the cable-stayed bridge under multiple support excitations have been examined to enhance a structure’s ability to withstand earthquake excitations. Comparison of the response due to non-uniform input ground motion with that due to uniform input demonstrates the importance of accounting for spatial variability of excitations. The performance of the optimized designed control systems for uniform input excitations gets worse dramatically over almost all of the evaluation criteria under multiple-support excitations.