Azo dyes play an important role in the printing and dyeing industry. Acid Black 2 dye is one of the most representative dyes with significant toxicity on human health and aquatic organisms. Accordingly, appropriate technologies are needed to efficiently remove these compounds from aqueous environment. In this study, we examined the electrochemical oxidation (EO) of Acid Black 2 on a boron-doped diamond anode. A Box–Behnken design was used to determine experimental factors, namely current density (A), electrolysis time (B), pH (C), and electrolyte concentration (D), and optimize responses to chemical oxygen demand (COD) removal (R1), current efficiency (R2), and energy consumption (R3). Based on obtained models, a desirability function approach to multiresponse optimization was used to optimize response values. The results of response values, R1 = 90.01%, R2 = 80.77%, and R3 = 83.51 kWh/kg (COD), were obtained at optimized conditions. Furthermore, the influence of interactions among operating parameters on responses was analyzed using analysis of variance and three-dimensional surface plots. Finally, an Acid Black 2 degradation pathway was proposed according to intermediates detected by HPLC-MS. In short, these results have certain guiding significance for the energy conservation, technology development, and practical engineering application of EO. [ABSTRACT FROM AUTHOR]