The purpose of this study was to determine the removal efficiency of ciprofloxacin (CIP) by the combined electrochemical–persulfate (EC–PS) process using iron electrodes. The effects of contact time, initial CIP concentration, persulfate (PS) concentration, pH and current density in CIP removal were investigated. To measure the CIP removal mechanisms in the EC–PS process, radical scavenger analysis, EDS and FTIR were performed on the EC–PS process and produced sludge, respectively. Based on the results obtained, the EC process after 160 min can remove 38% of CIP, while the PS process had no effect on CIP removal. In contrast, the EC–PS process under the optimum conditions: current density of 1.45 mA/cm2, PS concentration of 0.42 mM, pH of 5, CIP of 10 mg/L and contact time of 75 min, could reduce the antibiotic by more than 94%. Based on radical scavenger results, radical hydroxyl radicals play a major role in the EC–PS process. Also, by analyzing the results of radical scavenger, FTIR and EDS, it is suggested that the oxidation process was probably dominant in the early stages of the EC–PS process, and then, the electrocoagulation process played a basic role in CIP removal. The results of this study showed that the EC–PS process with a very good efficiency can be used to remove CIP antibiotics from aqueous solutions.