In this work the application of electrochemical anodic oxidation for the removal of the β-lactam antibiotic Oxacillin (OXA) was tested. The study was performed using an undivided stirred tank reactor equipped with a DSA (Ti/IrO2) anode and a zirconium spiral cathode. A statistical design of experiments was used to study the influence of different operating variables: substance concentration (6.0–1624.0 μmol L−1), current density (3.25–30.25 mA cm−2) and NaCl concentration (0.05–0.4 mol L−1). According to the Pareto chart, current density was the main variable influencing OXA degradation, followed by NaCl concentration. The effect of the initial pH and type of supporting electrolyte was also evaluated. The latter lead to the identification of different degradation routes which depended on the electrolyte employed. By using the best electrolyte and current density, complete OXA removal and total loss of antimicrobial activity was achieved after only 4 min of treatment. The efficiency in the oxacillin degradation was not significantly affected by the initial pH (3–9). Interestingly, no mineralization was observed even after long exposure times (8 h). However, 70% of the initial chemical oxygen demand (COD) was eliminated and the level of biodegradability (BOD5/COD) increased from 0.03 to 0.84, indicating that the system is able to transform the pollutant into highly oxidized and biodegradable bio-products with no antimicrobial activity. Additionally, different substances and radical scavengers present in wastewaters and natural water did not significantly affect the efficiency of the process. Finally, the more relevant initial aromatic by-products were identified and a degradation schema of the electrochemical oxidation of the OXA antibiotic was proposed.