There is an interdependent symbiotic relationship between humans and water; scientific and effective assessment of the human–water symbiosis relationship is of great significance for the promotion of sustainable development. This study developed a novel framework of the human–water symbiosis relationship under an integrated perspective, which included theoretical interpretation, quantitative assessment, pattern discrimination, and an attribution analysis. Based on the symbiosis theory, the theoretical analysis of the human–water relationship was carried out to analyze the three basic elements of the human–water system, and then the evaluation index system of the human–water symbiosis system was constructed to quantitatively assess the development level of the human system and the water system. The Lotka–Volterra model was used to identify the symbiotic pattern, and the human–water symbiosis index was calculated to characterize the health state of the human–water symbiosis system. The main influencing factors of the human–water symbiosis system were further identified through an attribution analysis. Finally, a case study was carried out with 18 cities in Henan Province. Results reveal that (a) the proposed method can effectively realize the quantitative characterization of the human–water symbiosis relationship, with good applicability and obvious advantages; (b) the human–water symbiosis pattern of cities in Henan Province is dominated by the “human system parasitizes water system (H+W−)” pattern, and more attention should be paid to the water system in the subsequent development of it; and (c) the main factors influencing the human system, the water system, and the human–water symbiosis system are the research and development (R&D) personnel equivalent full-time (H7), per capita water resources (W1), and proportion of water conservancy and ecological water conservancy construction investment (W6), respectively. The findings can provide theoretical and methodological support for the study of the human–water symbiosis relationship and sustainable development in other regions.