A copper-polyoxoniobate cluster (Cu-PONb) featuring Lewis acid/base dual sites was developed for the ultralow-energy mechanochemical synthesis of pharmacologically relevant 2-amino-3-cyano-4H-pyrans (ACPs). This solvent-minimized protocol enables an efficient, one-pot, three-component coupling of aldehydes, malononitrile, and diketones at room temperature with minimal energy input (e.g., 8 Hz oscillating frequency). The method exhibits exceptional substrate scope, scalability, and superior reactivity compared to conventional solution-phase approaches. Mechanistic studies reveal that the synergistic catalysis of Cu-PONb presents dual reaction pathways (Knoevenagel condensation followed by Michael addition/intramolecular cyclization), representing the first report of a mechanochemically driven polyoxometalate catalyst for ambient multicomponent reactions. This work presents a green and sustainable approach to accessing valuable bioactive heterocycles.