In the present study, PbO2 electrodes, doped with different doses of Er (0%, 0.5%, 1%, 2%, and 4%), were fabricated and characterized. Surface morphology characterization by SEM-EDS and XRD showed that Er was successfully doped into the PbO2 catalyst layer and the particle size of Er-PbO2 was reduced significantly. Electrochemical oxidation of sulfamerazine (SMR) in the Er-PbO2 anode system obeyed te pseudo first-order kinetic model with the order of 2% Er-PbO2 > 4% Er-PbO2 > 1% Er-PbO2 > 0.5% Er-PbO2 > 0% PbO2. For 2% Er-PbO2, kSMR was 1.39 h−1, which was only 0.93 h−1 for 0% PbO2. Effects of different operational parameters on SMR degradation in 2% Er-PbO2 anode system were investigated, including the initial pH of the electrolyte and current density. Under the situation of an initial pH of 3, a current density of 30 mA·cm−2, a concentration of SMR 30 mg L−1, and 0.2 M Na2SO4 used as supporting electrolyte, SMR was totally removed in 3 h, and COD mineralization efficiency was achieved 71.3% after 6 h electrolysis. Furthermore, the degradation pathway of SMR was proposed as combining the active sites identification by density functional calculation (DFT) and intermediates detection by LC-MS. Results showed that Er-PbO2 has great potential for antibiotic wastewater treatment in practical applications.