To address the issue that tetracycline antibiotic pollutants are accumulating in water and causing serious harm to human health and the ecological environment, this study prepared a novel composite material of CoFe_2O_4/MnO_2 and used it as a highly efficient permonosulfate (PMS) activator for the degradation of tetracycline hydrochloride (TCH) in the water body. The degradation results showed that the CoFe_2O_4/MnO_2-PMS system had outstanding TCH removal efficiency, which could reach 92.7% after 40 min of reaction, much higher than that of the single catalyst-PMS system. The results of the influencing factor experiments showed that the CoFe_2O_4/MnO_2-PMS degradation system had a wide range of pH suitability and a stable degradation activity in the presence of various anions. In addition, the CoFe_2O_4/MnO_2-PMS degradation system had good stability and reusability, showing high catalytic activity and TCH degradation rate after 5 cycles. Mechanistic analysis showed that the valence cycles of Co^2+/Co^3+, Fe^3+/Fe^2+ and Mn^3+/Mn^4+ existed in the CoFe_2O_4/MnO_2 composites to participate in the electron transfer process during the catalytic PMS degradation of TCH, leading to the full release of SO_4· and ·OH during the activation process and the effective degradation of TCH through a series of typical chain reactions.