For many engineered nanoparticles, the primary pathway of release into the environment is via sewage and industrial wastewater discharges. In this work, the removal of uncoated ZnO nanoparticles (ZnO NPs) during simulated wastewater treatment processes and its impact on treatment performance were examined. Simulated primary clarification removed the majority (about 70%) of the dosed ZnO NPs. During simulated sequencing batch reactor (SBR) processes, ZnO NPs were completely removed in each cycle throughout the 11-day experimental duration (two cycles per day). Continuous input of ZnO NPs into the wastewater (at concentrations up to 5 mg L−1) did not reduce chemical oxygen demand (COD) removal. NH4+-N removal was reduced at a dosing concentration of 5 mg L−1 ZnO NPs per cycle. Inhibition of respiration of nitrifying microorganisms by ZnO NPs corroborated the reduction of NH4+-N removal. These results indicate that if the wastewater is treated, the release of ZnO NPs into receiving water bodies would be minimal and ZnO NPs would mainly accumulate in biosolids. Uncoated ZnO NPs in wastewater at very high concentrations may have some adverse effects on activated sludge process.