The efficiency of oxygen evolution reaction (OER) depends critically on the steric and electronic structures of electrocatalysts. Moreover, a high conductivity of electrocatalysts ensures a fast electron transfer and thus plays a significant role in OER. Therefore, the development of efficient electrocatalysts with synergistically engineered structure and conductivity is urgently needed. Here, we present an ingenious design of manganese-modulated cobalt selenide nanosheets with systematically engineered structure and conductivity for efficient OER. Tailored atomic disorder, tuned electronic structure, and optimized electrical conductivity could be simultaneously realized by Mn modulation, leading to effective generation of active sites and promoted OER rate. The resultant (CoMn)Se-2 catalysts exhibited remarkable electrocatalytic OER performance with a 5.8-fold and 10.8-fold higher activity relative to CoSe2 and state-of-the-art IrO2. This work provides a comprehensive understanding on origin of high activity of transition metal non-oxide electrocatalysts and enables the rational design of highly efficient electrocatalysts with precisely engineered structural and electrical properties.