The two-dimensional layered double hydroxides (LDHs) and zero-dimensional metal clusters have emerged as promising nanomaterials in the field of sustainable water oxidation, which can also facilitate joint experimental and computational studies. In this study, the synthesis of Ni₆@LDH composites, comprising atomically precise Ni₆(MPA)₁₂ (MPA: mercaptopropionic acid) clusters embedded into LDH nanosheets via electrostatic interaction, represents a significant advancement in the development of nanomaterials for sustainable water oxidation. Ni₆@NiFe-LDH exhibits superior electrochemical performance in oxygen evolution reaction (OER), exhibiting OER overpotentials of 198 mV@10 mA·cm⁻² and 290 mV@100 mA·cm⁻² with a low Tafel slope of 29 mV·dec⁻¹. It surpasses the corresponding NiFe-LDH and commercial RuO₂ catalysts, primarily due to the synergistic interaction between Ni₆ clusters and LDHs. Interestingly, our combined experimental and computational approach reveals that the M-OOH_ads formation is the rate-determining step (RDS) for the Ni₆-based catalysts, differing from the RDS for NiFe-LDH itself (the M-O_ads formation). These efforts serve as an attempt to push forward the current research frontier to study structure–property relationships progressing from the micro-/nano-level to the precise atomic-level.