The oxygen reduction reaction (ORR) has emerged as an electrochemical approach for efficient fuel cells and metal-air batteries, which are promising and environmentally friendly strategies for achieving high-performance sustainable energy conversion and storage systems. Single-atom catalysts (SACs) have demonstrated significant potential for electrocatalytic ORR, which can be further enhanced by introducing heteroatom doping within the carbon matrix. However, the complex structure-function relationships between the doping positions and catalytic activity remains poorly understood. In this study, we synthesized Cu-based SACs comprising coordinated/uncoordinated S atoms on a nitrogen-doped carbon matrix. We introduced a ligand-modification strategy to precisely control the spatial distance between S dopants and the Cu active sites. Three different catalysts with distinct S positions were prepared and systematically evaluated for ORR. Furthermore, we systematically studied how the positions of S dopants affect catalytic behavior and set up structure-performance relationships for the first time. Operando Raman and X-ray absorption spectroscopy revealed the dynamic behavior of the catalytic Cu sites. In addition, density functional theory (DFT) calculations revealed a volcano-type relationship between the free energy (ΔG_OH*) and the Cu-S interatomic distance, highlighting an optimal S-doping configuration. This work provides deeper insights into the mechanistic role of the position of heteroatom in SACs, which is important for tuning their catalytic performance.