Highway bridges are important infrastructure components for the safety and functionality of any society. The immediate damage of highway bridges under hazard effects can disrupt transportation systems. It is of vital importance to assess the performance of bridges under natural hazards to aid the emergency response and recovery decision. Resilience, related to the functionality of structural systems under extreme events and the recovery patterns, is becoming a paramount performance indicator within the hazard management process. Resilience assessment of bridges under multiple natural hazards is emphasized in this paper. In addition, understanding how natural hazards affect the life-cycle performance of highway bridges can lead to improved preparedness prior to extreme disasters and benefit the society. A comprehensive framework for long-term loss and resilience assessment of highway bridges under multiple hazards is presented. A renewal process, a stochastic model for events occurring randomly in time, is developed to compute the long-term loss. The information obtained considering these metrics can be used in design, maintenance, and retrofit optimization processes of civil infrastructure systems under extreme events.