The development of highly active, selective, and stable electrocatalysts can facilitate the effective implementation of electrocatalytic CO conversion into fuels or chemicals for mitigating the energy crisis and climate problems. Therefore, it is necessary to achieve the goal through reasonable material design based on the actuality of the operational active site at the molecular scale. Inspired by the stimulating synergistic effect of coupled heteronuclear metal atoms, a novel Ni-Co atomic pairs configuration (denoted as NiN©CoN-NC) active site was theoretically screened out for improving electrochemical CO reduction reaction (CORR). The structure of NiN©CoN-NC was finely regulated by adjusting Zn content in the precursors Zn/Co/Ni-zeolite imidazolate frameworks (Zn/Co/Ni-ZIFs) and pyrolysis temperature. The structural features of NiN©CoN-NC were systematically confirmed by aberration-corrected HAADF-STEM coupled with 3D atom-overlapping Gaussian-function fitting mapping, XAFS, and XRD. The results of theoretical calculations reveal that the synergistic effect of Ni-Co atomic pairs can effectively promote the *COOH intermediate formation and thus the overall CORR kinetic was improved, and also restrained the competitive hydrogen evolution reaction. Due to the attributes of Ni-Co atomic pairs configuration, the developed NiN©CoN-NC with superior catalytic activity, selectivity, and durability, with a high turnover frequency of 2265 h at −1.1 V (vs. RHE) and maximum Faradaic efficiency of 97.7% for CO production. This work demonstrates the great potential of DACs as highly efficient catalysts for CORR, provides a useful strategy to design heteronuclear DACs, exploits the synergistic effect of multiple metal sites to facilitate complex CORR catalytic reactions, and inspires more efforts to develop the potential of DACs in various fields.