Proton exchange membrane fuel cells (PEMFCs), which have the advantages of high-power density, zero emission, and low noise, are considered ideal electrochemical conversion systems for converting hydrogen (H2) and oxygen (O2)/air into electricity. However, the oxygen reduction reaction (ORR), which is accompanied by multiple electrons, results in voltage loss and low conversion efficiency of PEMFCs. Currently, PEMFCs mainly use high-load precious platinum (Pt) to promote the ORR process; however, the high cost of Pt hinders the widespread commercialization of PEMFCs. Over the past few years, metal–nitrogen–carbon single-atom catalysts (M–N–C SACs) have attracted considerable attention and have been recognized as potential Pt-based catalysts owing to their outstanding ORR activity. This review briefly introduces the components of PEMFCs. Second, we discuss the catalytic mechanisms of the M–N–C SACs for the ORR. Third, the latest advances in noble, non-noble, and heteroatom-doped M–N–C SACs used as ORR and PEMFCs cathode catalysts are systematically reviewed. In summary, we have outlined the current challenges and proposed a future perspective of M–N–C SACs for PEMFCs cathodes.