Critical infrastructures are more exposed than ever to natural hazards in a changing climate. To understand and manage risk, failure cascades across large, real-world infrastructure networks, and their impact on people, must be captured. Bridging established methods in both infrastructure and risk modelling communities, we develop an open-source modelling framework which integrates a network-based interdependent infrastructure system model into the globally consistent and spatially explicit natural hazard risk assessment platform CLIMADA. The model captures infrastructure damages, triggers failure cascades and estimates resulting basic service disruptions for the dependent population. It flexibly operates on large areas with publicly available hazard, exposure and vulnerability information, for any set of infrastructure networks, hazards and geographies of interest. In a validated case study for 2018’s Hurricane Michael across three US states, the model reproduced important failure dynamics among six infrastructure networks, and provided a novel spatial map where people were likely to experience disruptions in access to healthcare, loss of power and other vital services. Our generalized approach allows for a view on infrastructure risks and their social impacts also in areas where detailed information and risk assessments are traditionally scarce, informing humanitarian activities through hotspot analyses and policy frameworks alike.