In this study, the adsorption of roxarsone (ROX) onto corncob-derived activated carbon (AC) was optimized using response surface methodology (RSM). Following this, the AC was comprehensively characterized by FT-IR, SEM, and EDS analysis. The results showed that the highest ROX adsorption efficiency of 304.34 mg/g was obtained at the contact time of 262 min, initial pH of 2.5, adsorbent dosage of 0.4 g/L, and initial concentration of 240 mg/L. Besides, it was found that the adsorption equilibrium data was fitted well to the Langmuir and Sips isotherm models. The thermodynamic parameters (e.g., ΔG, ΔH, and ΔS) revealed the spontaneous and exothermic nature of ROX adsorption. As indicated by pseudo second-order kinetics model, the adsorption of ROX onto AC could be achieved through the hydrogen bond, π-π adsorbate-adsorbent interaction, and electrostatic interaction between AC surface functional group and molecular species variations of ROX at different pH values. Overall, it can be concluded that corncob-derived AC is an alternative option for removing ROX from aqueous solution.