Differences of Sexual Development (DSDs) are amongst the most common birth defects in humans. Alarmingly, the incidence of DSDs has increased significantly in the last few decades, and this rise is attributed to our increased exposure to endocrine disrupting chemicals (EDCs). Furthermore, some EDCs are predicted to have far reaching effects beyond the exposed individual, causing disease that persists over multiple generations. Our research examines the effects of estrogenic EDCs on reproductive development and fertility in both males and females over multiple generations. We have examined the effects of diethylstilbestrol (DES), a clinically relevant EDC, across four generations of mice. DES caused a significant reduction in anogenital distance, reproductive organ weights and fertility, and an increased incidence of DSDs through to the F4 generation. A significant difference in maternal and paternal lineages was also observed in males for body weight, seminal vesicle weight, seminiferous tubule diameter and hypospadias rate. This data has significant implications for multiple generations of DES descendants. Furthermore, the impacts described from exposure of pregnant mothers to EDCs raises concerns about the effects of exposures to multiple estrogenic EDCs present in our environment.