This study presents a strategy to remove tetracycline by using magnetite-activated persulfate. Magnetite (Fe3O4) was synthesized at high purity levels-as established via X-ray diffractometry, transmission electron microscopy, and N2 sorption analyses-and tetracycline was degraded within 60 min in the presence of both magnetite and persulfate (K2S2O8), while the use of either substance yielded limited degradation efficiency. The effects of magnetite and persulfate dosage, the initial concentration of tetracycline, and the initial pH on the oxidative degradation of tetracycline were interrogated. The results demonstrate that the efficiency of tetracycline removal increased in line with magnetite and persulfate dosage. However, the reaction rate increased only when increasing the magnetite dosage, not the persulfate dosage. This finding indicates that magnetite serves as a catalyst in converting persulfate species into sulfate radicals. Acidic conditions were favorable for tetracycline degradation. Moreover, the effects of using a water matrix were investigated by using wastewater treatment plant effluent. Comparably lower removal efficiencies were obtained in the effluent than in ultrapure water, most likely due to competitive reactions among the organic and inorganic species in the effluent. Increased concentrations of persulfate also enhanced removal efficiency in the effluent. The tetracycline degradation pathway through the magnetite/persulfate system was identified by using a liquid chromatograph-tandem mass spectrometer. Overall, this study demonstrates that heterogeneous Fenton reactions when using a mixture of magnetite and persulfate have a high potential to control micropollutants in wastewater.