ABSTRACT Estimating the loss of life resulting from dam failures is required for devising emergency action plans and strategies for alert issuance and evacuation. However, current models for simulating fatalities are computationally expensive, forced by highly uncertain variables, and not readily interpretable, which may limit their use in engineering and research. For circumventing these problems, we utilize the polynomial chaos expansion technique (PCE) for approximating the loss of life as obtained from the agent-based model LifeSim and propagating uncertainty of inputs, namely, alerted population, mobilized population, alert issuance, and hazard identification, to the model responses. We also benefit from the PCE spectral representation for assessing the effects of each input in the loss of life associated with the dam failure in an urban area in Brazil, considering efficient and inefficient scenarios for alert and evacuation. The PCE error ranged from 10–3 to 10–2, and the mean squared error between the metamodel output and LifeSim was between two fatalities. In global sensitivity analysis, the variables alert issuance and hazard identification contributed the most to the number of fatalities. These findings provide objective guidelines for implementing more effective safety measures, potentially reducing loss of life resulting from a dam break in the study area.