Transgenerational effects of microcystin-LR (MC-LR) released by cyanobacterial blooms have become a hot topic. In the present study, adult zebrafish pairs were exposed to 0, 0.4, 2, and 10 μg/L MC-LR for 60 days and the embryos (F1 generation) were hatched without or with continued MC-LR exposures at the same concentrations until 5 days postfertilization (dpf). The results showed the existence of MC-LR both in F0 gonads and in F1 embryos and indicated that MC-LR could be transferred directly from the F0 adult fish to F1 offspring. The adverse effects on sex hormone levels, sexual development, and fecundity in F0 generation along with abnormal development in F1 offspring were observed. Furthermore, downregulation of antioxidant genes (cat, mn-sod, gpx1a) and upregulation of innate immune-related genes (tlr4a, myd88, tnfα, il1β) as well as increased proinflammation cytokine contents (TNF-α, IL-1β, IL-6) were noticed in F1 offspring without/with continued MC-LR exposures. In addition, significant differences between the two F1 embryo treatments demonstrated that continuous MC-LR exposure could result in a higher degree of inflammatory response compared to those without MC-LR exposure. Our findings revealed that MC-LR could exert cross-generational effects of immunotoxicity by inhibiting the antioxidant system and activating an inflammatory response.