In recent decades, climatic and anthropogenic pressures have caused serious environmental problems. The joint analysis of geo-environmental variables, through geoprocessing techniques, can support the estimation of the contribution of each environmental component to hydro-environmental fragility (HF). The aim of this work was to analyze the contribution of climatic phenomena and deforestation in the HF of the Gurupi River Watershed (GRW). Precipitation data were extracted from the Climate Hazards Group InfraRed Precipitation with Stations (CHIRPS); land use and cover were obtained from the MapBiomas Project; drainage network was acquired from the National Water and Sanitation Agency (ANA); slope data were gathered from the National Institute for Space Research (INPE); soil data were obtained from the Brazilian Agricultural Research Corporation (EMBRAPA); geomorphological units were extracted from the Brazilian Institute of Geography and Statistics (IBGE); and rock data were based on the Geological Survey of Brazil (CPRM). For the mapping of HF, the Analytic Hierarchy Process (AHP) was adopted to weigh the importance of each variable in four extreme precipitation year scenarios (1989, 2012, 2015, and 2019). It was observed that spatial precipitation is considerably different in extreme years. Results showed that deforestation has increased over the years; and that static geo-environmental variables (drainage, slope, soils, geomorphological units, and rocks) have larger feature domains that favor the increase of HF in the GRW. The HF of the GRW showed significant differences in the analyzed scenarios. Policies and environmental conservation programs are needed in the GRW.