The purpose of the study is to determine the effects of multiple support excitations (MSE) and soil-structure interaction (SSI) on the dynamic characteristics of cable-stayed bridges founded on pile foundation groups. In the design of these structures, it is important to consider the effects of spatial variability of earthquake ground motions. To do this, the time histories of the ground motions are generated based on the spatially varying ground motion components of incoherence, wave-passage, and site-response. The effects of SSI on the response of a bridge subjected to the MSE are numerically illustrated using a three-dimensional model of Quincy Bayview cable-stayed bridge in the USA. The soil around the pile is linearly elastic, homogeneous isotropic half space represented by dynamic impedance functions based on the Winkler model of soil reaction. Structural responses obtained from the dynamic analysis of the bridge system show the importance of the SSI and the MSE effects on the dynamic responses of cable-stayed bridges.