Electrochemical oxidation of 5-hydroxymethylfurfural (HMF) has shown promising prospects in producing highly valuable chemicals. Herein, we report the synthesis of ultrasmall Ag nanoclusters anchored on NiCo-layered double hydroxide (NiCo-LDH) nanosheet arrays (Agn@NiCo-LDH) via a facile electrodeposition strategy. The prepared Agn@NiCo-LDH nanosheet arrays exhibit excellent electrocatalytic HMF oxidation performance with a current density of 10 mA cm−2 at 1.29 VRHE and the Faraday efficiency of nearly 100% for 2,5-furandicarboxylic acid production. This study offers an effective approach to rationally design nanoclusters to achieve high catalytic activity for sustainable energy conversion and production.