The use of zinc oxide nanoparticles (ZnO NPs) and polybrominated diphenyl ethers (PBDPEs) in different products and applications leads to the likelihood of their co-occurrence in the aquatic system, making it important to study the effect of PBDPEs on the fate and transport of ZnO NPs. In this study, we determine the influence of PBDPEs (BDPE-47 and BDPE-209) on the colloidal stability and physicochemical properties of ZnO NPs in different aqueous matrices. The results indicated the shift in ζ potential of ZnO NP from positive to negative in the presence of both PBDPEs in all tested waters; however, the effect on the NPs surface potential was specific to each water considered. The lower concentration of the PBDPEs (e.g., 0.5 mg/L) significantly reduced the ζ potential and hydrodynamic diameter (HDD) of ZnO NP, even in the presence of high content of dissolved organic matter (DOM) in both freshwater and industrial wastewater. Moreover, both BDPE-47 and BDPE-209 impede the agglomeration of ZnO NP in simple and natural media, even in the presence of monovalent and polyvalent cations. However, the effect of BDPE-47 on the ζ potential, HDD, and agglomeration of ZnO NP was more pronounced than that of BDPE-209 in all tested waters. The results of Fourier transform infrared (FT-IR) and X-ray Photon Spectroscopy (XPS) further confirm the adsorption of PBDPEs onto ZnO NP surface via aromatic ether groups and Br elements. The findings of this study will facilitate a better understanding of the interaction behavior between the ZnO NPs and PBDPEs, which can reduce the exposure risk of aquatic organisms to both pollutants.