Unplanned urbanization increases the exposure of people to environmental hazards. Within a landscape ecology framework, this study is a diagnosis of human health risk in San Martín, an urban district of Buenos Aires, Argentina. Risk was estimated by combining four hazard indexes (water and air pollution, and mosquito and rodent infestation) and a vulnerability index. Each index was obtained by integrating environmental and socio-demographic layers in a Geographic Information System. Spatial autocorrelation was assessed for each hazard, vulnerability and risk indexes using Moran’s tests. Also, spatial associations between pairs of variables were addressed by means of Geographically Weighted Regressions. The robustness of hazard and vulnerability indexes was checked by a sensitivity analysis. In General San Martń district, 83.3% of the population is exposed to relatively high levels of at least one hazard; 7.4% is exposed to relatively high levels of all hazards (11.5% of the total area) and only 16.7% lives in areas of relatively low levels of all hazards (15.4% of the total area). Areas where hazard intensity was relatively high corresponded to those areas where the most vulnerable population lives, enhancing human health risk. The models for hazards and vulnerability were reasonably robust to changes in the weights of the variables considered. Our results highlight the spatially heterogeneous nature of human health risk in an urban landscape, and reveal the location of critical risk hotspots where reduction or mitigation actions should be focused.