Electrochemical CO2 reduction (CO2R) represents a sustainable way to store intermittent renewable energies and produce carbon-neutral fuels, yet the energy efficiency remains a huge bottleneck owning to its sluggish kinetics and complex reaction pathways. Highly active, selective, and robust electrocatalysts are strongly demanded to accelerate CO2 conversion and deploy this technology to practical applications. In this review, we focus on single-atom catalysts (SACs), a unique category of electrocatalysts with atomically dispersed metal active sites, which have shown distinctive performances in CO2R and offer an ideal platform for in-depth mechanistic studies at the atomic level. Despite various SACs with attractive CO2R performances have been reported, the relationship between electronic/geometric structure of SACs and the corresponding electrocatalytic performance still needs to be discussed with caution. Here we take a broad overview on the recent progress in understanding the structure–function correlation of SACs in CO2R, with the purpose of providing deep insights and guiding the future rational design of SACs. First, we provide the fundamental understandings of CO2R on SACs, following different reaction pathways. Then, we describe the progresses in the development of well-defined SACs and the mechanistic studies on the influences from particular structural parameters, such as first-shell and second-sphere coordination, conductive supports and interface with a secondary catalyst. Finally, some perspectives are highlighted on the path towards efficient CO2R on SACs.