Engineered nanomaterials (ENMs), such as copper oxide nanoparticles (CuO NPs), are emerging as pollutants extensively used in many commercial and industrial applications, thus raising environmental concerns due to their release into water bodies. It is, therefore, essential to remove these pollutants from water bodies in order to minimize the potential threat to the aquatic environment and human health. The objective of this study was to investigate the removal of CuO NPs from waters by the coagulation process. This study also explored the efficiency of coagulation to remove hydrophobic/hydrophilic dissolved organic matter (DOM) and turbidity with varying polyaluminum chloride (PACl) doses. According to the results, a high concentration of DOM affects both the CuO NPs zeta potential and hydrodynamic diameter, thereby decreasing the agglomeration behavior. At effective coagulation zone (ECR), high removal of CuO NPs (>95%) was observed for all studied waters (hydrophobic and hydrophilic waters), above ECR excess charge induced by coagulant restabilized particles in solution. Furthermore, waters containing hydrophobic DOM and those with high UV254nm values needed more coagulant dose than hydrophilic waters to obtain similar CuO NP removals. The primary mechanism involved in CuO NPs removal might be charge neutralization. These findings suggest that PACl is an effective coagulant in the removal of CuO NPs; however, water characteristics are an influencing factor on the removal performance of ENMs during the coagulation process.