Electrochemical synthesis of hydrogen peroxide (H2O2) through 2e– oxygen reduction reaction is an effective approach to replace anthraquinone process. However, most reported electrocatalysts work effectively in alkaline medium in which H2O2 will easily decompose into water. It is still of great challenge to develop cost‐effective electrocatalysts with high activity and selectivity for electrocatalytic H2O2 production in acidic media. Herein, it is first theoretically demonstrated that the adsorption energy of OOH* intermediate on carbon can be optimized by embedding Co nanoparticles (Co NPs) and tuning oxygen‐containing functional groups, ensuring high activity and selectivity. Guided by density functional theory calculations, highly porous open carbon nanocages with embedded Co NPs are designed and synthesized by template‐engaged method. The pyrolysis temperature can effectively modulate the electronic and pore structure of carbon nanocages. Impressively, the optimized carbon nanocages synthesized at 700 °C (P‐Co@C‐700) with highest percentage of –C–O–C group and defects, largest specific surface area (1351 m2 g–1), and mesoporous structure exhibit high selectivity up to 94% toward H2O2 production in 0.1 m HClO4. Furthermore, the P‐Co@C‐700 nanocages display promising application for efficient electro‐Fenton degradation of model organic pollutant. The density functional theory calculations predict that the adsorption energy of OOH* on carbon can be optimized by embedding Co nanoparticles and tuning oxygen‐containing functional groups for the electrosynthesis of H2O2. Guided by calculations, open carbon nanocages with optimized electronic and pore structures are synthesized, manifesting high selectivity up to 94% for H2O2 synthesis in 0.1 m HClO4.