The electrocatalytic oxidation of methane (CH₄) facilitates the direct conversion of abundant natural gas into value-added chemicals utilizing renewable electricity. However, the high dissociation energy of the C–H bond and the presence of multiple competing reaction pathways lead to poor product selectivity. We synthesized a Ni-based polyoxometalate (Ni-POM-V_O) through cluster-nucleus co-assembly and introduced rich oxygen vacancies using N₂ cold plasma etching. The optimized catalyst attained a Faradaic efficiency of 88.4% for ethanol at 1.7 V versus the reversible hydrogen electrode (RHE). Notably, the oxygen vacancies in Ni-POM-V_O create Lewis acid sites that enhance methane adsorption and activation, thereby facilitating its conversion into *CH₂ and *CH₂OH intermediates. The subsequent adsorption of these intermediates onto the polyoxometalate (POM) framework promotes C–C coupling, resulting in ethanol production. This work provides a new method for adjusting the Lewis acid content on the catalyst surface through oxygen vacancies, improving the selectivity of methane electro oxidation to ethanol.