Irregular multi-span continuous bridges with unequal height piers are commonly adopted in mountainous areas when crossing steep-sided valleys. As common practice, economical unbonded laminated rubber bearings and concrete shear keys are usually installed in such bridges as superstructure-to-substructure connections. In strong earthquakes, the sliding of rubber bearings and the shear key failure are mostly expected, which may weaken the seismic resistance of the irregular bridges. The current study is mainly divided into three parts: the first one investigates the effect of concrete shear keys on the transverse seismic performance of the irregular bridges by incorporating the potential sliding of laminated rubber bearings; the second part proposes the concept of using yielding steel dampers to replace shear keys for mitigating the irregular seismic responses of the unequal height bridges with the practical design method being developed; the third part demonstrates the retrofit effectiveness by conducting nonlinear time-history analyses. The results indicate that the existence of concrete shear keys increases the bridge irregularity by inducing a significant in-plane superstructure rotation response around the vertical axis, posing nonuniform displacement demands at the substructures. The shear keys also contribute to the unbalanced ductility demands on the unequal height substructures, rendering the taller piers more vulnerable to the seismic damages. This differs from the case with fixed bearings, where the shorter piers are more subjected to damages. Using yielding steel dampers that are appropriately designed as per the proposed method, the seismic rotations of the bridge superstructure can be considerably mitigated with a relatively uniform superstructure movement maintained. The steel dampers are also effective in distributing the inertia forces among the unequal height piers. The effectiveness of yielding steel dampers replacing concrete shear keys in unequal height irregular bridges is successfully verified by the results from the numerical simulation.