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Climate change and rural depopulation are changing the ecological and hydrological cycles in China. Data on the normalized difference vegetation index (NDVI), temperature, precipitation, streamflow, sediment and rural population are available for the Gan River basin from 1981 to 2017. We investigated the spatio-temporal variations in climate, human activity and vegetation mainly using the Mann–Kendall test and examined their relationship using the Granger causality test. The results showed that (1) the temperature markedly increased in all seasons; (2) the precipitation increased in summer and winter but decreased in spring and autumn; (3) overall, the NDVI increased markedly during 2005–2017, but showed seasonal differences, with decreases in summer and winter and increases in spring and autumn; (4) the annual sediment transport showed a significant decreasing trend and (5) a large number of the population shifted from rural to urban areas, resulting in a decrease in the rural population between 1998 and 2018. Rural depopulation has brought about farmland abandonment, conversion of farmland to forests, which was the factor driving the recovery of the vegetation and the decrease in sediment. The results of this study can provide support for climate change adaptation and sustainable development.