Freshwater systems are subjected to multiple anthropogenic stressors and natural disturbances that act as debilitating agents and modifiers of river systems, causing cumulative and synergistic effects that deteriorate their health and result in watershed vulnerability. This study proposes an easy-to-apply spatial method of watershed vulnerability evaluation using Geographic Information Systems (GIS) in the Andalien River watershed, located in the Chilean mediterranean. A watershed vulnerability index (WVI) based on three sub-indices-anthropogenic stressors, environmental fragility and natural disturbances - was developed. To determine the index grouping weights, expert surveys were carried out using the Delphi method. We subsequently normalized and integrated the factors of each sub-index with relative weights. The ranges of each thematic layer were re-classified to establish vulnerability scores. The watershed was divided into three sections: headwaters zone, transfer zone and depositional zone. The watershed vulnerability index showed that 41% of the watershed had very low vulnerability and 42% had medium vulnerability, while only 1% - in the depositional zone - had high vulnerability. A one-way ANOVA was carried out to analyze the vulnerability differences among the three sections of the watershed; it showed significant differences (F (2, 16) = 8.15: p < 0.05). The a posteriori test showed differences between the headwaters and depositional zones (Tukey test, p = 0.005) and between the transfer and depositional zones (Tukey test, p = 0.014). To validate the WVI, water quality was measured at 16 stations in the watershed; there was a significant correlation between vulnerability level and NO2- levels (r = 0.8; p = 0.87; alpha = 0.05) and pH (r = 0.8; p = 0.80; alpha = 0.05). The WVI showed the cumulative effects of multiple stressors in the depositional zone of the watershed. This is the first study to evaluate and validate non-regulated watershed vulnerability with GIS using multiple anthropogenic and natural stressors. (C) 2018 Elsevier B.V. All rights reserved.