•Modeled corrosion-fatigue degradation to assess life-long performance of RC bridges.•Rebar pitting corrosion and traffic-induced fatigue stresses form this degradation.•Degrading bridges are analyzed for earthquakes with substantial vertical components.•FE model of the bridge is updated at every life-cycle year to capture degradation.•Results portray higher life-cycle seismic vulnerability of all critical components. Highway bridges, located in heavy traffic and corrosive environments, are prone to corrosion-fatigue degradation, due to which material properties of steel and concrete in bridge girders get altered and effective area of rebars reduces resulting in reduced flexural stiffness of girders. Consequently, exposed bridges become weaker to resist earthquake loads, particularly for the ones having three significant translational components. It is, therefore, important to evaluate life-long performance of bridges that suffer from corrosion-fatigue degradation and are subjected to seismic events having substantial vertical ground motions (VGMs). Such a threatening scenario for seismic safety of bridges has not been explored yet. The current study demonstrates the confronting role of corrosion-fatigue degradation and VGM on bridge seismic response through a representative multi-span RC bridge in Gujarat, India, and required information on corrosion, traffic, and seismic activities is acquired from appropriate sources. The degradation mechanism is modeled as a coupled phenomenon of pitting corrosion of rebar and traffic-induced fatigue stresses that give rise to fatigue cracks at deep pit locations of rebars in girders. Developed numerical model of the bridge composes of all essential features to accurately capture the gradual degradation along life-span and fluctuations in response of key vulnerable bridge components under horizontal and vertical excitations. Results suggest that ignoring the impact of this degradation mechanism and VGM can lead to higher seismic vulnerability of bridges and endanger their safety under future earthquakes.