AbstractAbundant active sites and their easy accessibility in a stable and conductive structure are of great importance for efficient electrocatalysts. In principle, activated mesoporous single‐crystal microparticles can meet these desired requirements. Here, the Fe‐doped NiS2 mesoporous single crystal microparticles decorated with FeS clusters on the pore walls (FeS@MSC‐NiS2:Fe) are constructed via a pre‐decorated and sequentially seeded mesoporous silica template. Throughout the external and internal surfaces, the Fe‐doped NiS2 modulated by the adjacent FeS clusters induces favorable charge distributions and promotes the crucial formation of the active Fe/Ni (oxy)hydroxide. Combined with the spatial enrichment effect of the intermediates in the holey space and the boosted charge transfer within the continuous single‐crystalline framework, the dually regulated FeS@MSC‐NiS2:Fe as ideal integral microreactors show efficient performances in oxygen evolution reaction. In electrochemical tests, the particulate FeS@MSC‐NiS2:Fe requires an overpotential of only 236 mV to reach a current density of 10 mA cm−2 and displays fast reaction kinetics with a Tafel slope of 32.4 mV dec−1. This study provides an important strategy to construct electrocatalysts with highly active sites and good accessibility.