The highly hazardous chemical ammonia has been proven to be absorbed by nanoparticles, thereby exerting highly toxic effects on aquatic organisms. As a ubiquitous pollutant in aquatic environments, polystyrene nanomicroplastics (PSNPs) have shown strong adsorption capacity due to their large surface area. Therefore, the potential joint effects of ammonia and PSNPs need to be clarified. In this study, zebrafish embryos were exposed to a water solution with ammonia concentrations (0, 0.1, 1, and 10 mg/L) with or without PSNP (100 μg/L) treatment up to 120 hpf. The results showed that combined exposure increased the accumulation of ammonia and obviously reduced the locomotor speed of zebrafish larvae compared with exposure to ammonia alone. Further studies indicated that PSNPs can aggravate ammonia-induced neurotoxicity by altering the cholinergic system, dopaminergic neurons, and the retinal structure in zebrafish larvae. In addition, our results revealed that ammonia caused significant alterations in the expression of genes related to neurodevelopment and retinal development, and PSNPs exacerbated this adverse effect. In conclusion, PSNPs can aggravate ammonia-induced neurotoxicity in the early stage of zebrafish and their associated health risk to aquatic animals should not be underestimated. The main contribution of this article lies in revealing the synergistic neurotoxicity of ammonia and PSNPs in the early stage of zebrafish. Moreover; it emphasizes that the associated health risks to aquatic animals should not be underestimated.