Water resources play an essential role in socioeconomic development, and the evaluation of water resources vulnerability is conducive to regional development and sustainable utilization of water resources. Based on the analytical framework of vulnerability scoping diagram (VSD), we developed a composite water resources vulnerability evaluation system from exposure, sensitivity and adaptability dimensions. Subsequently, a comprehensive spatiotemporal analysis of water resources vulnerability in Guangdong Province over the period of 2010-2022 was carried out by means of trend analysis and spatial autocorrelation method. The results show that water resources vulnerability showed a distribution pattern of “high in the south and central; low in the north, east and west”. The core region of the Pearl River Delta presented the highest level of water resources vulnerability, followed by the east and west Guangdong; whereas the north Guangdong exbibited the lowest. In the study period, the water resources vulnerability of most cities in Guangdong Province has decreased; while that of Shenzhen has increased. The water resources vulnerability of Guangdong Province exhibited a positive spatial autocorrelation and there was a strengthening trend in spatial agglomeration. High-high clustering areas were mainly distributed in the Pearl River Delta region, while low-low clustering areas in the north and west Guangdong. This study clarified the distribution pattern of water resources vulnerability in Guangdong Province, so as to provide a guide for decision-making of sustainable water resources management.