In this study, the electrocatalytic synergy of the graphite/β-PbO2 anode and granular activated carbon (GAC) particles electrodes for bisphenol A (BPA) degradation are investigated in a three-dimensional electrochemical reactor (3DER). The graphite/β-PbO2 anode was prepared by anodic deposition method and the electrocatalytic properties of lead oxide film were studied by FESEM, XRD, EDX-mapping, linear sweep voltammetry and accelerated lifetime test techniques. The effect of five independent variables including pH, Na2SO4 concentration, current density, GAC amount, and reaction time on the system response was optimized by an orthogonal central composite-genetic algorithm (OCCD-GA). The results showed that β-PbO2 crystals were deposited as completely compact pyramidal clusters on the graphite surface. In addition, the service life and oxygen evolution potential (OEP) for the electrocatalytic layer of β-PbO2 were 90 h and 2 V, respectively. Based on the developed quadratic model (R2 > 0.99 and p-value < 0.0001), the optimal points for pH, Na2SO4 concentration, current density, GAC amount, and reaction time were predicted to be 4.6, 0.074 mol L−1, 35.7 mA cm−2, 25 g, and 80 min, respectively. Under optimal conditions, BPA removal efficiency in 3DER system and separate application of electrocatalytic degradation and GAC were obtained 98.8%, 72.2% and 9.75%, respectively. Thus, the electrocatalytic synergy of 3DER system due to lead oxide layer and GAC particle electrodes in BPA degradation was calculated to be 35.5%. LC-MS analysis was used to identity the intermediates formed during BPA degradation. The final degradation intermediates were short-chain acids including adipic acid, malonic acid and, acetic acid.