Wesselsbron virus (WSLV) is a neglected, mosquito-borne flavivirus that is endemic to the African continent. The virus is teratogenic to ruminants and causes a self-limiting febrile illness in humans. Wesselsbron disease manifests with similar clinical signs and occurs in the same areas under the same climatic conditions as Rift Valley fever, which is therefore included in the differential diagnosis. Although the gross pathology of WSLV infection in pregnant ewes is reported in literature, the pathogenesis that leads to stillbirths, congenital malformations and abortion has remained undescribed. In the present study, pregnant ewes were inoculated with WSLV and subjected to detailed clinical- and histopathology 8 days later. The virus was mainly detected in foetal trophoblasts of the placenta and in neural progenitor cells, differentiated neurons, oligodendrocytes, microglia and astrocytes. Our study demonstrates that WSLV efficiently crosses the maternal–foetal interface and is highly neuroinvasive in the ovine foetus.