With the intensification of climate change, understanding the impacts of climate change on the water cycle is vital for integrated watershed management. Based on the precipitation and temperature data from 1980 to 2018, the climatic change characteristics of the Three Gorges Reservoir Area were analyzed. The Soil and Water Assessment Tool (SWAT) was used to simulate the spatial and temporal distribution of runoff and water quality. The result indicated that precipitation showed clear inter-annual fluctuation, and the maximum and minimum temperatures showed an increasing trend with rates of 0.38 °C/10a and 0.29 °C/10a, respectively. The moving averages revealed that the annual averages of runoff, total nitrogen (TN), and total phosphorus (TP) loads showed a decreasing trend followed by an increasing trend, which experienced strong inter-annual fluctuations. The hydrological processes changed significantly at different spatial scales, and the most affected area was the middle and head of reservoir area. The highest correlation was found between precipitation and runoff (0.91), followed by TP (0.81), and TN (0.60), while extreme precipitation could result in a high probability of water pollution events. These findings provide useful information to support the utilization of water resources, especially in the face of strong climate change impacts.