Chloramphenicol (CAP) is a broad-spectrum antibiotic widely used in animal farming and aquaculture industries. Despite its ban in many countries around the world, it is still used in several developing countries, with harmful effects on the surrounding aquatic environment. In this study, an electrooxidation process using a Ti/PbO anode was used to investigate the degradation of CAP in both synthetic solution and real aquaculture wastewater. A central composite design was used to determine the optimum conditions for CAP removal. Current intensity and treatment time had the most impact on the CAP removal. These two factors accounted for ∼90% of CAP removal. The optimum conditions found in this study were current intensity of 0.65 A, treatment time of 34 min, and CAP initial concentration of 0.5 mg L. Under these conditions, 98.7% of CAP removal was achieved with an energy consumption of 4.65 kW h m. The antibiotic was not present in the aquaculture wastewater, which received 0.5 mg L of CAP and was treated (by electrooxidation) under the optimum conditions. A complete removal of CAP was obtained after 34 min of treatment. According to these results, electrooxidation presents an option for the removal of antibiotics, secondary compounds, and other organic and inorganic compounds from solution.