<p>Highway bridges are often designed with extended pile-shafts due to their cost-effectiveness compared to conventional pile foundations. In contrast to pile foundations that generally remain elastic during earthquakes, extended pile-shafts have similar diameters to columns and are susceptible to localized seismic damage below ground. The complexity stems from column-pile-shaft-soil interactions, variations in soil properties, and bridge-specific design details. This study develops a comprehensive framework to evaluate the seismic fragility of highway bridges supported by extended pile-shafts, advancing the state of the art in several aspects. First, high-fidelity three-dimensional soil-shaft-column-bridge models are developed and validated in OpenSees, enabling the systematic integration of all critical components and capturing multi-directional seismic responses. Second, a two-stage cyclic pushover analysis procedure is conducted to elucidate the column-shaft coupling effect and develop capacity limit state models tailored specifically for extended pile-shafts. Third, uncertainties in bridge attributes and soil profiles are incorporated through Latin Hypercube Sampling, alongside the Kullback-Leibler (KL) divergence measurement to determine the required sample size for reliable fragility estimation. Fourth, for the first time, this study examines the impact of depth-varying ground motions on the seismic demands of different bridge components. Finally, a direct fragility comparison between pile-shaft and pile-group bridges reveals critical differences in stiffness distribution, load transfer mechanisms, and resulting seismic vulnerabilities. Collectively, the developed component- and system-level fragility models provide essential insights for seismic risk assessment, damage inspection, and performance-based design of highway bridges with extended pile-shafts.</p>