With the in-depth promotion of the water control idea of “giving priority to water conservation, space balance, systematic governance and two-handed power”, in order to improve the current water control level, it is of great significance to evaluate the regional total factor water resources utilization efficiency scientifically and effectively in China, analyze its differences, and explore its influencing factors. This paper calculated the regional water footprint in China and brought it into the input-output analysis framework. On this basis, the Shephard water resources distance function was constructed, and combined with SFA model, the total factor water resources utilization efficiency in China from 2003 to 2018 was calculated. The results showed that: The total amount of water footprint in China showed a fluctuating upward trend, and the growth trend gradually slowed down after 2010. There were significant differences in the average value and average annual growth rate of regional water footprint. The regional total factor water resources utilization was inefficient, with the characteristics of high in the east and low in the west. The whole country and the east, middle, and west all showed a W-shaped change trend of decline-rise-decline-rise. There was a U-shaped relationship between environmental regulation and total factor water resources utilization efficiency. In the long run, strengthening the intensity of environmental regulation was conducive to improving the total factor water resources utilization efficiency. Economic development level, technical level, trade structure, industrial structure and water use structure had positive promoting effects on China’s total factor water resources utilization efficiency, while urbanization had negative promoting effects. The scale of foreign capital failed to pass the significance test. Based on the research conclusion, the paper puts forward corresponding countermeasures, including speeding up the optimization of industrial structure, and adjusting the upgrading of industrial structure according to local conditions based on the carrying capacity of local water resources environment.