Compared with acidic environments, promoting the water dissociation process is crucial for speeding up hydrogen evolution reaction (HER) kinetics in alkaline electrolyte. Although the construction of heterostructured electrocatalysts by hybridizing noble metals with metal (hydr)oxides has been reported as a feasible approach to achieve high performance, the high cost, complicated fabrication process, and unsatisfactory mass activity limit their large-scale applications. Herein, we report a single-phase HER electrocatalyst composed of single-atom ruthenium (Ru) incorporated into a cobalt oxide spine structure (denoted as Ru SA/Co3O4), which possesses exceptional HER performance in alkaline media via unusual atomic-scale Ru–Co pair sites. In particular, Ru SA/Co3O4 exhibits a very low overpotential of 44 mV at 10 mA cm–2 and an outstanding mass activity of 4700 mA mg–1 at 50 mV overpotential, superior to those of commercial Pt/C, Ru nanoparticles supported on Co3O4 (denoted as Ru NP/Co3O4) and other reported Ru-based electrocatalysts. With insights from theoretical calculations, the synergistic interactions between Ru and Co pair active sites in Ru SA/Co3O4 are revealed to catalyze diverse fundamental steps of the alkaline HER; i.e., the Ru sites can effectively accelerate water adsorption/dissociation and OH– desorption, whereas the Co sites are favorable for H* adsorption and H2 evolution.