As an emerging area, single-atom catalysts (SACs), in the past decade, have sparked tremendous research interests in various fields due to maximum atom utilization and excellent catalytic activity. Recently, SACs have been extended to peroxymonosulfate (PMS)-mediated advanced oxidation processes for organic wastewater remediation. In the current perspective, we first briefly overviewed typical synthetic methods and characterization techniques for metal–organic framework (MOF)-derived SACs. Then, we highlighted the degradation applications of various refractory organic pollutants via SAC/PMS systems. Subsequently, the catalytic mechanisms as well as the variety of reactive species were discussed. Finally, we proposed several future development directions for MOF-based SACs in environmental remediation.