The utilization of sulfate radical-based advanced oxidation processes (SR-AOPs) has captivated the academic community due to their minimal energy requirements and superior efficacy in peroxomonosulfate (PMS) activation for pollutant decomposition. Notwithstanding these advantages, engineering an effective and economical catalyst for PMS activation presents a considerable hurdle. In the present study, a metal-organic framework of CoFe PBA is ingeniously anchored onto g-C3N4 nanosheets, resulting in the formation of an innovative CoFe PBA/g-C3N4 S-scheme heterojunction that demonstrates remarkable efficiency in PMS activation. Intriguingly, the catalytic efficiency of CoFe PBA/g-C3N4 surpasses that of g-C3N4 and CoFe PBA by 7-fold and 2.33-fold, respectively. The heightened activity of CoFe PBA/g-C3N4 heterojunction is attributed to the enhanced charge transfer efficiency, a consequence of the successful heterojunction formation. Concurrently, the ability of photoexcited electrons to reduce Co3+/Fe3+ to Co2+/Fe2+ bolsters PMS activation. Significantly, this heterojunction retains unparalleled stability in degrading oxytetracycline without discernible performance attenuation, heralding its commendable prospects in real-world applications. Besides, mechanism exploration indicates that SO4−, h+, and electron transfer contribute to oxytetracycline degradation in the CoFe PBA/g-C3N4 system. This investigation serves as a beacon for the strategic development of highly active and stable catalysts for PMS activation, aiming at environmental decontamination.