Perfluorobutanesulfonate (PFBS) is increasingly polluting aquatic environments due to worldwide manufacturing and application. However, toxicological knowledge regarding PFBS exposure remains scarce. Here, we showed that PFBS life-cycle exposure at environmentally realistic concentrations (0, 1.0, 2.9, and 9.5 μg/L) skewed the sex ratio in fish toward male dominance, while reproductive functions of female fish were greatly impaired, as characterized by extremely small ovaries, blocked oocyte development, and decreased egg production. Endocrine disruption through the hypothalamus-pituitary-gonad axis was induced by PFBS exposure, showing antiestrogenic activity in females but estrogenic activity in males. PFBS was found to gradually accumulate in F0 adults during continuous exposure but can be rapidly eliminated when depurated in clean water. Parental exposure also transferred PFBS pollutant to F1 offspring eggs. Although no trace of PFBS was detected in F1 adults and F2 eggs, adverse effects from parental exposure persisted in F1 and F2 offspring. These transgenerational effects implicate PFBS as an ongoing threat to the fitness and sustainability of fish populations. The dramatic impairment of fish reproduction highlights the urgency of re-evaluations of the ecological and evolutionary consequences of PFBS exposure. Copyright © 2019 American Chemical Society.