Focusing on water resources related sustainable development goals (SDGs), a localized water resources sustainability evaluation index system was constructed, and the entropy weight method was used to evaluate the sustainable development level of water resources in Guangdong Province and its 21 prefecture-level cities. Then, the current situation and historical evolution of water resources sustainability in Guangdong Province were analyzed. The results show that the water resources comprehensive sustainability in Guangdong Province increased slowly from 2010 to 2019, with obvious differences of sustainability in time, space, and goals, and the sustainability was high in the core region of the Pearl River Delta, but low in eastern and western Guangdong Province; the ecological environment system had the highest support for sustainability, followed by the water resources system and efficiency system, and the equity system had the weakest influence; the improvement of water supply and storage capacity, as well as the continuous improvement of water resources utilization efficiency, promoted the enhancement of water resources sustainability, while water ecological degradation, water environment deterioration, and spatial imbalance of water allocation tended to be the most important limiting factors of water resources sustainable development. In addition, the water-use efficiency goal (SDGs6.4) had the highest sustainability, the water quality improvement goal (SDGs6.3), water ecological restoration goal (SDGs6.6), and freshwater ecosystem protection goal (SDGs14.1) obviously lagged behind, and the goals of integrated water resources management improvement (SDGs6.5) and terrestrial ecological environment restoration (SDGs15.1) were at an intermediate level. In general, water resources comprehensive sustainability was characterized by the coexistence of efficiency advantage and integrated disadvantage of water quality, pollution, and ecology.