Taking the Guangdong-Hong Kong-Macao Great Bay Area as the study object, the harmonious relationship between human and water in nine cities of Guangdong from 2014 to 2018 was quantified based on human-water harmony theory, and its spatiotemporal distribution characteristics was analyzed. The three factors of health, development and coordination degree were taken into consideration in establishing an index evaluation system. The comprehensive weights were determined using subjective and objective weights and cooperative game theory, with which the values of these three factors were calculated and the human-water harmony degree was assessed. The results show that the human-water harmony of the nine cities ranked from “almost harmonious” to “quasi harmonious”, developing to “harmonious” level. The relationship between human and water in the three cities of Jiangmen, Zhaoqing and Huizhou around the Greater Bay Area was slightly higher than that in the others, which alleviated the pressure of highly concentrated development on the water resources system and provided high-quality water resources for the future development of the Great Bay Area.