Abstract: The ecological protection and high-quality development of Yellow River Basin constitute a major national strategy, however, water scarcity has become the greatest constraint to its development. As an important unconventional water resource, mine water possesses significant strategic potential to alleviate regional water shortages by fully exploiting its resource attributes. In addition, by reducing the direct discharge of mine water, it mitigates pollution risks to surface water environments. Nonetheless, the overall utilization level of mine water remains low and unevenly distributed across regions. Based on a systematic analysis of the characteristics and utilization status of mine water resources in Yellow River Basin, a strategic framework for their protection and use is explored. The findings reveal notable regional disparities: the mine water inflow intensity exhibits a gradient increase from west to east along the basin; the total inflow volume shows a spatial pattern of higher values in the central region and lower values at both ends; water quality displays a gradient with a high degree of mineralization upstream, complex types midstream, and relatively better quality downstream. Based on the relative relationship between coal production and mine water inflow, four typical patterns have been identified: “high production-low discharge”, “low production-high discharge”, “balanced production and discharge”, and “low production-low discharge.” Mine water utilization rates vary widely, ranging from less than 30% to over 90%, with industrial use dominating the utilization structure, while ecological and agricultural uses remain underdeveloped. Drawing on advanced international experiences, a four-dimensional coordinated strategic framework—“spatial, functional, temporal, and institutional”—is established, forming a full-chain layered governance system characterized by “source reduction, harmless treatment during processes, resource recovery at the tail end, and terminal recharge.” Key projects are deployed, including precise emission reduction and pollution control engineering, intelligent mine water monitoring networks, quality-based hierarchical treatment systems, innovative utilization models, and regional recharge storage with groundwater remediation, alongside safeguard measures such as policies and regulations, collaborative governance, and technological innovation. Ultimately, the transition of mine water in Yellow River Basin from an “environmental burden” to a “strategic resource” is promoted, providing solid water resource security for regional ecological protection and high-quality development.