Copper oxide nanoparticles (CuONPs) have received tremendous attention as efficient adsorbents owing to their low cost, desirable surface area, abundant active sites, potent textural characteristics and high adsorption capacities. However, CuONPs have not been employed to decontaminate water laden with increasing environmental contaminants such as thiazolyl blue and paracetamol. Herein, the adsorption of thiazolyl blue and paracetamol onto green synthesized CuONPs prepared from the aqueous leaf extract of Platanus occidentalis was studied. The BET, SEM, FTIR, XRD, EDX and pH point of zero charge showed the successful synthesis of CuONPs having desirable surface properties with a surface area of 58.76 m2/g and an average size of 82.13 nm. The maximum monolayer adsorption capacities of 72.46 mg/g and 64.52 mg/g were obtained for thiazolyl blue and paracetamol, respectively. The Freundlich, pseudo-second-order and intraparticle diffusion models were well fitted to the adsorption of both pollutants. The pH studies suggested the predominance of electrostatic and weaker intermolecular interactions in the adsorption of the thiazolyl blue and paracetamol, respectively. Spontaneous, physical, endothermic and random adsorption of the pollutants on CuONPs was obtained from the thermodynamic consideration. The biosynthesized CuONPs were found to be highly reusable and efficient for the adsorption of thiazolyl blue and paracetamol from water.