AbstractRecent findings reported in the contemporary literature have underlined the criticality of including climate change effects in models of deterioration of civil engineering structures. Highway bridges, when exposed to unfavorable environmental conditions and climate change settings and when simultaneously situated in moderately to highly active seismic zones, may experience reduced structural performance during earthquake events. For bridges in such regions, past studies have revealed the criticality of considering deterioration when computing seismic losses, which may constitute a significant percentage of the life-cycle cost planning for the structure. In acknowledging the potential effects of climate change on bridge deterioration and seismic fragility, a renewed systematic assessment of seismic life-cycle cost then becomes necessary for informed decision making and economic investment. Addressing this critical need, we propose a novel framework for evaluating the lifetime seismic losses of highway bridges that considers earthquake hazards, aging effects, and global warming due to climate change. The proposed framework was first demonstrated on two structurally distinct case-study bridges––multispan continuous (MSC) steel and MSC concrete-girder bridges located in the southeastern United States. Both bridge types comprise multiple seismically vulnerable bridge components that are also prone to the adverse effects of environmental degradation. It was found that there was a substantial underprediction in the lifetime seismic loss––by 6.7% for the MSC steel bridge and 13.2% for the MSC concrete bridge––when expected future climate change was neglected. Additionally, the proposed framework was applied to a seismically designed MSC concrete-girder bridge in order to evaluate the influence of seismic design practices on the lifetime seismic losses of aging highway bridges, including climate change effects.