2,4,6-Trichlorophenol (2,4,6 TCP) is one of the hazardous toxicants, which has severe impacts on the environment and human health. This study is designed to develop a highly sensitive and selective electrochemical sensor based on CuO nanostructures for the detection of 2,4,6 TCP. The CuO nanostructures were synthesized through an aqueous chemical growth method and characterized by versatile analytical techniques, for example, Fourier transform infrared spectroscopy, field emission scanning electron microscopy, atomic force microscopy, energy-dispersive spectrometry, and X-ray diffraction. The characterization tools revealed a high crystalline nature, exceptional phase purity, nanoball morphology with an average size of around 18.7 nm for the CuO nanostructures. The synthesized material was used to modify a glassy carbon electrode (GCE) with the help of Nafion as a binder to improve its efficiency and sensitivity. The CuO/Nafion/GCE was proven to be a potential sensor for the determination of 2,4,6 TCP under optimized conditions at a scan rate of 70 mV/s, potential range of 0.1-1.0 V, and phosphate buffer of neutral pH as the supporting electrolyte. The linear range for 2,4,6 TCP was set from (1 to 120 mu M) with a low limit of detection value calculated to be 0.046 mu M. The developed sensor was effectively applied for water samples with acceptable recovery values from 95.9 to 100.6%.