Global fishery resources have been declining for decades, leading some fisheries to collapse. Although the decline is partly due to man-made chemical contamination, causal chemicals have been identified in only a few cases. We conducted consecutive 3-year investigations of embryonic mortality in Taihu Lake, China, including heavily contaminated northern areas, including Zhushan (ZS), Meiliang (ML), and Gonghu (GH), and the less polluted southeastern Suzhou (SZ). In 2016, 65.8% of crucian carp (Carassius carassius) embryos collected from ZS died before hatching, a substantially higher mortality rate than those observed in ML (21.7%), GH (15.2%), and SZ (2.2%). In 2017, the embryonic mortality rates were 38.8% in ZS, 1.3% in ML, 6.9% in GH, and 3.5% in SZ, and these rates strongly correlated with the concentrations of tris(1,3-dichloro-2-propyl)phosphate (TDCIPP): 104.2, 1.8, 4.6, and 4.1 ng/g lipid weight (lw) in embryos from ZS, ML, GH, and SZ, respectively. In 2018, embryonic mortality decreased to 4.0% in ZS and 1.2% in GH, consistent with decreases in embryonic TDCIPP concentrations to 17.1 and 1.5 ng/g lw, respectively. Moreover, the TDCIPP concentrations in dead embryos (70.5−216.8 ng/g lw) were much higher than those in live embryos (1.2−10.5 ng/g lw). Embryonic mortality was also observed in well-controlled laboratory experiments in which wild crucian carp were exposed to TDCIPP at concentrations similar to those measured in embryos collected from Taihu Lake, thus confirming TDCIPP as a causal factor in mass crucian carp embryo mortality in Taihu Lake. TDCIPP thus poses a threat to the sustainability of fisheries worldwide, given the high worldwide production volume of this chemical and its embryonic lethal toxicity.