The situation of resource utilization and eco-environment protection remains critical globally. The harmony between eco-environment health and water-energy utilization efficiency is a strong support for the realization of high-quality development. In this paper, an Assessment-Decoupling two-stage framework was developed to investigate the relationship between water-energy resource utilization and ecological security. In detail, an improved input-output indicator system was constructed to assess the water-energy resource utilization efficiency (WEUE), and its influencing factors were examined from multiple system perspectives; then, we intended to evaluate the ecological risk (ER) from a raster-scale perspective based on land-use types; and finally, the decoupling idea was introduced to quantify the fitness relationship of the above two aspects. The framework was applied to Henan Province, China. The study found that: (1) the WEUE of Henan Province shows a “W” pattern of development during 2000–2020; in 2000–2010, the WEUE of South Henan declined, while in 2010–2020, the WEUE of Henan Province gradually improved, with significant increases in various districts. (2) The ecological risk index (ERI) in Henan Province generally shows a decreasing trend, and the spatial difference is more obvious, with the high-risk areas mainly concentrated in the central, east, and south Henan, and the west of Henan is mainly a low-risk area. (3) There is strong spatial variation in the decoupling states of WEUE and ERI of the 18 districts in Henan Province, and the differences become more pronounced over time. The number of districts with a strong negative decoupling state has been increasing during the entire period, and a total of 14 districts have reached the above state in 2020. The developed framework offers a new idea for clarifying the relationship between resource utilization and ecological conditions, and the obtained results can provide data support for the realization of sustainable development.