A semiempirical approach considering the rate of reactive chlorine species-RCS- production (ΦE) as a function of current and Cl− concentration for the modeling of acetaminophen (ACE) degradation is presented. A filter-press reactor having a Ti/RuO2–ZrO2 (Sb2O3 doped) anode, NaCl (0.04–0.1 mol L−1) as supporting electrolyte, and operated in continuous mode, was considered. A current of 100 mA and a flow of 11 mL min−1 favored the electrogeneration of RCS and ACE degradation. Hydraulic retention time and ΦE were the most relevant parameters for the RCS production. These two parameters, plus the pollutant concentration, were very determinant for the ACE degradation. The model successfully reproduced the ACE removal in distilled water at different concentrations (10, 20, 40, and 60 mg L−1). The electrochemical system achieved removals between 80 and 100% of ACE in distilled water. The ACE treatment in actual seawater (a chloride-rich matrix, 0.539 mol L−1 of Cl−) was assessed, and the degradation was simulated using the developed model. The competing role toward electrogenerated RCS by intrinsic organic matter (3.2 mg L−1) in the seawater was a critical point, and the simulated values fitted well with the experimental data. Finally, the action of the electrochemical system on ciprofloxacin (CIP) in real seawater and its antimicrobial activity was tested. CIP removal (100% at 120 s) was faster than that observed for ACE (100% of degradation after 180 s) due to CIP has amine groups that are more reactive toward RCS than phenol moiety on ACE. Moreover, the system removed 100% of the antimicrobial activity associated with CIP, indicating a positive environmental effect of the treatment.