The conflict of the human-water relationships (HWR) has further increased the water-related risks, such as water environment deterioration, water shortages, and even regional violent conflicts for obtaining usable water resources. Knowing how to evaluate and regulate the discordant HWR to form a balanced growth between sustainable socio-economy and water resources protection has become a critical issue in water resources management. The harmony theory method, which provides a new perspective for solving the conflict between humans and water, has been widely used in current studies. However, this method focuses less on the quantitative study of the balance status of HWR. This study proposes a harmony theory-based HWR evaluation method that contains a systematic process of harmony assessment, indicator identification, harmony balance constraints, and harmony regulation for assessing and regulating the discordant HWR. The Henan Province of China, which has a complicated HWR, was selected as a case study to apply and verify the approach proposed in this study. The results indicated that (1) Henan Province showed a poor harmony status. The human–water harmony degree of 18 distinctions in the province varied from 0.41 to 0.76, showing an increasing trend from 2006 to 2018, indicating that the HWR was gradually improving in recent years. (2) The human–water harmony degree showed that HWR in the southwest part of Henan Province, with less human activities, was better than that in its northeast part, which had faster social development. Sanmenxia City, located in the west part of the province, had the highest human–water harmony degree because of the recent water control projects implemented in the city, indicating that human production measures could effectively help improve HWR. (3) At present, Henan Province has serious discordant indicators in these three aspects (water system health, humanistic system development, and human-water system coordination), which proves that it is still facing pressure from both socio-economy sustainable development and water resources protection. Our results provide insight into water resources management in Henan Province and other similar regions.