Study regionThe study area is located in the Nukus irrigation area on the lower reaches of the Amudarya River in Uzbekistan. Study focusThe extensive agricultural land development has introduced a substantial amount of water resources into the irrigation area, leading to a significant rise in regional groundwater levels. Quantifying regional groundwater resource issues and achieving sustainable groundwater management under conditions of high spatiotemporal heterogeneity are key scientific issues for regional ecological protection. Thus, this study used the concept of ecological water level to quantify groundwater issues, used the MIKE-SHE hydrological model to conduct scenario simulations, formulated and subsequently evaluated a groundwater regulation plan with spatiotemporal attributes. New hydrological insights for the regionRegional sustainable development groundwater level should be within the range of 1.78–2.78 m. During the irrigation and non-irrigation periods, the groundwater levels in approximately 84.3 % and 72.2 % of the study area respectively exceeded the upper and lower ecological water level limits. Under the background of gradually increasing groundwater fluctuations, it will pose a serious threat to regional ecology. Therefore, this paper established a monthly-scale groundwater zoning control plan, which can make the area of regional groundwater within the ecological water level reach 87.53 %. All research not only contributes to the protection of the local ecological environment but also provides valuable insights for water resources management in other regions.