Oropouche virus (OROV) is an emerging arbovirus currently spreading across South America, with increasing reports of neurological manifestations, severe systemic disease, and congenital abnormalities. Although traditionally associated with mild febrile illness, the recent geographic expansion and surge in OROV outbreaks have prompted attention to its neurotropic potential. We investigated the effects of OROV infection on neural development using neural stem cells (NSCs) and brain organoids derived from human induced pluripotent stem cells, using a novel reassortant OROV isolate and a prototypical strain. OROV infected NSCs efficiently, leading to widespread cell death, depletion of proliferative progenitors, and disruption of neuroepithelial organization. Transcriptomic profiling revealed reduction of antiviral response genes and enrichment of signaling pathways related to viral replication, apoptosis, and inhibition of stem cell maintenance and neuronal differentiation. These molecular signatures aligned with phenotypic collapse of progenitor pools and cortical structure observed in organoids, in which OROV infected progenitors, neurons and astrocytes. Proteomic analysis of brain organoids infected with OROV showed regulation of neurodevelopment pathways, which have been previously associated with ZIKV infection, suggesting a common mechanism to reduced growth of infected cerebral organoids by ZIKV and OROV and highlighting their potential to impair brain development.These results reveal a previously unrecognized neuroteratogenic potential of OROV strains and provide mechanistic insight into their potential to induce microcephaly-like phenotypes, highlighting OROV as a significant threat to maternal-fetal health.