Zearalenone (ZEN), a mycotoxin with endocrine disruptive activity and oxidative stress generating ability, has been a worldwide environmental concern for its prevalence and persistency. However, the long-term effect of ZEN on aging process is not fully elucidated. Thus, the present study applied the Caenorhabditis elegans model to investigate the aging-related toxic effect and possible underlying mechanisms under prolonged and chronic ZEN exposure. Our results showed that locomotive behaviors significantly decreased in ZEN (0.3, 1.25, 5, 10, 50 μM) treated C. elegans. In addition, lifespan and aging markers including pharyngeal pumping and lipofuscin were also adversely affected by ZEN (50 μM). Furthermore, ZEN (50 μM) increased ROS level and downregulated antioxidant genes resulted from inhibition of nuclear DAF-16 translocation in aged C. elegans, which was further confirmed by more significant aging-related defects observed in ZEN treated daf-16 mutant. In conclusion, our findings suggest that the aging process and aging-related decline were induced by long-term exposure of ZEN in C. elegans, which is associated with oxidative stress, inhibition of antioxidant defense, and transcription factor DAF-16/FOXO.