A simplified grillage bridge model suitable for parametric study of skew bridge is presented, and the formulae for computing the seismic response of skew bridges are developed. Considering the existence of crossbeams and elastic bearings, the effects of stiffness eccentricity ratios, frequency ratios, the number of beams and skew angles are assessed using response spectrum analysis. The results show that the natural frequencies and mode shapes depend mainly on the stiffness eccentricity ratio and frequency ratios. The study also demonstrates that the seismic response of skew bridge is influenced quite noticeably by stiffness eccentricity ratio and frequency ratio. The maximum seismic response of skew bridge can be reduced by increasing stiffness eccentricity ratio and frequency ratio. Based on this study, a theory to evaluate the dynamic behavior and seismic response of skew bridges is presented and it can be conveniently applied in bridge seismic design.