In this work, an Fe3O4 catalyst was synthetized in a single step via electrochemical synthesis. The Fe3O4 catalyst was used to evaluate the degradation of Ofloxacin (OFX) using a heterogeneous advanced oxidation process with sodium persulfate (PS). PS activation was successfully achieved via thermal conventional heating directly and subsequently applied for the degradation of OFX. The degradation kinetics were studied under different conditions, such as catalyst and oxidant concentration and temperature. The results show that a higher reaction temperature, catalyst and initial PS dose strongly influence the degradation efficiency. Thermal activation of persulfate was tested at 20, 40 and 60 °C. At 60 °C, the half-time of OFX was 23 times greater than at 20 °C, confirming the activation of persulfate. Mineralization studies also showed that under optimized conditions (20 mM of persulfate, 1 g/L catalyst and 100 mg/L OFX), a 66% reduction in organic matter was observed, in contrast to that obtained at 40 °C and 20 °C, which was null. The reusability, as tested through the fourth reuse cycle, resulted in a 38% reduced degradation efficiency when comparing the first and last cycle. Furthermore, the electrosynthesized catalyst presented similar degradation efficiencies in both real water and MilliQ, mainly because of the Cl2− generation at high Cl− concentrations that takes place in Cl− contaminated water.