Copper oxide with activated carbon-based materials was synthesized for the selective detection of amoxicillin (AMX) in aqueous samples. The morphological and structural characteristics of the materials were evaluated using a scanning electron microscope and X-ray diffraction. Electrochemical impedance spectroscopy and voltammetric techniques were also used to observe the electrochemical response of the system. The best AMX sensing behavior was obtained with the presence of copper oxide that interacts with AMX and the increased surface area of activated carbon, which results in a sharp oxidation current. The electrode showed two linear responses in the AMX concentration ranges from 10 μM to 100 μM and from 1mM to 5mM, respectively. In the linear ranges, the sensitivity of the sensing materials was calculated to be 9.5528Ω μM-1 and 0.14994Ω μM-1, respectively. The statistical test confirms that the electrode showed good repeatability and selectivity in the determination of AMX.