Abstract Based on multi-support excitation theory, an irregular C-shaped curved bridge model with high piers was made by taking scale proportion of 1:20 to conduct the seismic simulation shaking table test in this paper. Failure mode of high flexible piers and earthquake damage mechanism of the curved bridge with high piers in action of different seismic wave spectrum, different peak acceleration, and different local topography effect were studied. The results showed that the failure mode of high flexible pier presents obvious distributional flexible characteristics, #1 pier’s cracks concentrated in range of 0.125L–0.46L (L is the height of the piers) from the bottom of the pier, while #2 and #3 pier’s cracks concentrated in range of 0.07L–0.625L from the bottom of the piers. Pier elevation difference significantly affected pier cracks development and bridges dynamic response. Accompanied with increase of load, the fundamental frequency curve presented decline in leveling off, while the damping increased gradually and the capacity of seismic energy dissipation of the structure enhanced. Dynamic responses of the curved bridge are different and presented different law when four different seismic waves were applied. When seismic loads increased from 120 gal to 360 gal, peak dynamic response basically presented linear growth. When seismic loads increased from 480 gal to 960 gal, considering the local topography effect, peak dynamic response significantly presented nonlinear growth. In action of seismic load of 960 gal, the displacements at the top of the #1 and #3 piers were up to 32.3 mm, showing that the seismic response was relatively large at head and tail section of bridge thus prone to cause beam dropping down.