[Objective] Current research on groundwater reserves in China primarily focuses on northern regions. Key challenges remain regarding the relationship between groundwater reserves and routine-emergency water supply, the construction of reserve systems, and the principles for reserve utilization. Focusing on the middle reaches of the Yangtze River—a region with favorable groundwater reserve conditions, dense urban distribution, and insufficient urban water supply security under extreme conditions—this study explores the connotation, hierarchical framework, and utilization strategies of groundwater reserves. The aim is to mitigate extreme water scarcity threats and enhance urban water supply security. [Method] Groundwater reserve volume was defined as the volume of groundwater stored to address water supply security threats in routine systems caused by extreme droughts or emergencies. The risks of extreme droughts and sudden pollution events, urban water supply security capacity, and groundwater occurrence and utilization in the middle reaches of the Yangtze River were analyzed. On this basis, a hierarchical groundwater reserve framework (HWUSR) was innovatively constructed based on five dimensions: crisis level of urban water supply security (How), urban scale (Where), reserve purpose (Use), reserve area scale (Scale), and groundwater renewability (Renewability). [Results] (1) Extreme droughts occur frequently in the middle reaches of the Yangtze River, severely threatening urban water supply systems that rely primarily on surface water. The region possesses massive groundwater storage, which can resolve the insufficient water supply security capacity for critical towns during extreme water scarcity events. (2) Groundwater reserves in important towns with abundant groundwater and low exploitation rates should follow a hierarchical approach. Priority should be given to megacities with dense populations and developed industries, as well as pilot zones with strong economic foundations, high population density, primary reliance on surface water, and inadequate emergency supply capacity. Domestic water needs for urban residents should be prioritized over industrial demands. Shallow aquifers with good water quality, high extractability, and strong renewability should be prioritized for reserves. (3) The utilization of groundwater reserves should adhere to the principles of confirmed necessity, dedicated use, shallow-deep complementarity, appropriate utilization, post-use recovery, and dynamic early warning. (4) Strategic reserve utilization must clarify responsibilities, implementation entities, timing, plans, and evaluations of effectiveness and environmental impacts. Following the principle of “whoever utilizes compensates, whoever benefits restores”, compensation and restoration measures must be implemented post-utilization. [Conclusion] These findings provide an important reference for the formulation and implementation of the groundwater reserve system and the construction of reserve demonstration projects in the Yangtze River Basin.