The oxygen evolution reaction (OER) represents the rate-determining step of electrocatalytic water splitting into hydrogen and oxygen. Creating oxygen vacancies and adjusting their density has proven to be an effective strategy to design high-performance OER catalysts. Herein, a hydrogenation method is applied to treat a two-dimensional (2D) iron-cobalt oxide (Fe1Co1Ox-origin), with the purpose of tuning its oxygen vacancy density. Notably, compared with Fe1Co1Ox-origin, the iron-cobalt oxide hydrogenated at 200 °C and 2.0 MPa optimized conditions exhibits a markedly improved OER activity in 1.0 M KOH (with an overpotential η of 225 mV at a current density of 10 mA·cm–2) and a rapid reaction kinetics (with a Tafel slope of 36.0 mV·dec–1). Moreover, the OER mass activity of the hydrogenated oxide is 1.9 times that of Fe1Co1Ox-origin at an overpotential of 350 mV. The experimental results, combined with density functional theory (DFT) calculations, reveal that the optimal control of oxygen vacancies in 2D Fe1Co1Ox via hydrogenation can improve the electronic conductivity and promote OH– adsorption onto nearby low-coordinated Co3+ sites, resulting in a significantly enhanced OER activity.