Differences of Sexual Development (DSDs) are amongst the most common birth defects in humans. A rise in the incidence of these disorders has been linked to our increased exposure to endocrine disrupting chemicals (EDCs). In addition, some EDCs are predicted to have far reaching effects beyond the exposed individual, causing disease that persists over multiple generations through alterations to the epigenome. Our study aimed to determine if estrogenic EDCs interfere with the establishment of the germ cell epigenome to cause impacts that persist in subsequent generations. We have examined the effects of diethylstilbestrol (DES), a clinically relevant EDC, across three generations of male mice and analysed the rates of reproductive disorders. A decline in several reproductive parameters including fertility rates, was detected through to the F3 generation in the male descendants of DES exposed mice. A number of DSDs, such as hypospadias and epispadias, were also increased in F1, F2 and F3 generations. This study suggests that exposure of pregnant mothers to DES has direct effects on the developing young, including epigenetic changes to their fetal germ cells, that result in the long-term transgenerational inheritance of male reproductive disorders.