The seismic performance of lead-rubber bearings (LRBs) is significantly affected by both the axial force and loading rate they experience. Accurate assessment of LRBs’ seismic performance, therefore, requires realistic simulation of these forces and rates, as well as of the response of the isolated structure during seismic events. This study conducted a series of real-time hybrid simulations (RTHS) to evaluate the seismic behavior of LRBs in such conditions. The simulations focused on a two-span continuous bridge isolated by LRBs atop the central pier, exposed to horizontal and vertical ground motions. In the RTHS framework, the LRBs were physically tested in the laboratory, while the remainder of the bridge was numerically modeled. Findings from these simulations indicated that the vertical ground motion had a minimal effect on the lateral response of the bridge when isolated by LRBs.