Water supply services (WSSs) are critical to human survival and development. The Integrated Valuation of Ecosystem Services and Trade-offs (InVEST) model enables an integrated, dynamic, and visual assessment of ecosystem services at different scales. In addition, Geodetector is an effective tool for identifying the main driving factors of spatial heterogeneity of ecosystem services. Therefore, this article takes the Three Gorges Reservoir Area (TGRA), the most prominent strategic reserve of freshwater resources in China, as the study area and uses the InVEST model to simulate the spatiotemporal heterogeneity of the supply-demand balance of WSSs and freshwater security patterns in 2005, 2010, 2015, and 2018, and explores the key driving factors of freshwater security index (FSI) with Geodetector. The total supply of WSSs in the TGRA decreased by 1.05% overall between 2005 and 2018, with the head and tail areas being low-value regions for water yield and the central part of the belly areas being high-value regions for water yield. The total demand for WSSs in the TGRA increased by 9.1%, with the tail zones and the central part of the belly zones being the high water consumption areas. In contrast, the head zones are of low water consumption. The multi-year average FSI of the TGRA is 0.12, 0.1, 0.21, and 0.16, showing an upward trend. The key ecological function areas in the TGRA are high-value FSI regions, while the tail zones in the key development areas are low-value FSI regions. Industrial water consumption significantly impacts FSI, with a multi-year average q value of 0.82. Meanwhile, the q value of industrial and domestic water consumption on FSI in 2018 increased by 43.54% and 30%, respectively, compared with 2005. This study analyzes the spatiotemporal variation of WSSs and detects the drivers in the natural-economic-social perspective and innovation in ecosystem services research. The study results can guide water resource security management in other large reservoirs or specific reservoir areas.