Abstract A reversible H 2 O‐responsive system based on Mg −2 ‐coordinated copper nanoclusters (CuNCs) is constructed. The dual effect of Mg²⁺‐ligand coordination and H 2 O‐induced hydrogen bonding leads to a thousand‐fold fluorescence enhancement. The quantum yields (QY) increase from 0.9% to 74.5% for the 2‐methylthiourea (MTU) system, and from 0.4% to 20.7% for the thiourea (TU) system, respectively. Notably, yellow‐emitting Y‐Mg‐CuNCs@TU (568 nm) transforms to red‐emitting R‐Mg‐CuNCs@TU (612 nm) upon drying, accompanied by structural changes. Characterizations confirm the crucial roles of coordinated Mg, hydrogen bonding, and lattice H 2 O. The transformation is reversible for over 13 cycles by alternating hydration/dehydration, demonstrating high potential for advanced information encryption applications.