This paper describes a novel electrode material, diclofenac-impregnated mesoporous carbon modified with a cationic surfactant, cetyltrimethylammonium bromide (DF-CMK-3/CTAB), for ultratrace analysis of the arsenic drug roxarsone (ROX). DF-CMK-3 amorphous carbon is a material with a high specific surface area and well-defined, hexagonally ordered, thin mesopores. The functional groups attached to the carbonaceous surface, such as chromene and pyron-like oxygen groups, lactam, and aromatic carbon rings, have the basic character and they can donate electrons. Modification of DF-CMK-3 with a CTAB layer significantly increases the analytical signal due to electrostatic interactions between the cationic surfactant and the anion form of ROX in the acidic medium. The voltammetric procedure at the glassy carbon sensor modified with DF-CMK-3/CTAB exhibited excellent sensitivity (limit of detection of 9.6 × 10−11 M) with a wide range of linearity from 5.0 × 10−10 to 1.0 × 10−4 M. Analysis of real samples (treated municipal wastewater and river water) showed recoveries from 96 to 102% without applying the complicated sample pretreatment step. The sensor demonstrated excellent sensitivity in the analysis of the arsenic drug ROX in the presence of interferences in environmental water samples.