Seismic safety of highway bridges is one of the critical issues for the functionality of transportation lifelines after severe earthquakes. Skewed highway bridges are found to be more vulnerable due to the irregular distribution of seismic demands on the bridge components. Moreover, scour induced loss of soil material and hence reduction in lateral support around the foundation piles can amplify the seismic effects on the structural components of water crossing bridges. A numerical study was conducted to investigate the seismic performance of skewed and straight highway bridges with varying scour depths and two different scouring types around the bridge piles. Analytical models of straight (0°) and 45° skewed bridges were created using the OpenSees program and a series of nonlinear response history analysis was carried out under the effect of recorded strong ground motions. In the first scouring type which was called as Case-1, scour depth was assumed the same around all piles and varied uniformly. In Case 2, two different non-uniform scouring types with linearly varying scour depth around the piles were investigated. The uncertainty in the earthquake ground motion excitation direction of the two horizontal components was also studied by considering the variable incidence angle of ground motion pairs. The maximum seismic demands of the members at different ground motion incidence angles were evaluated and compared to the demands obtained for the critical ground motion incidence angles suggested by Caltrans. Superstructure displacement, curvature demands of bridge column and shear force demands of pile elements are the seismic demand parameters examined within the scope of the study and were compared for each scour condition for both straight (0°) and 45° skewed bridge.