Persistent organic pollutants (POPs) are ubiquitous in the environment and display the capacity to bioaccumulate in living organisms, constituting a hazard to both wildlife and humans. Although restrictions have been applied to prohibit the production of several POPs since the 1960s, high levels of these compounds can still be detected in many environmental and biological matrices, due to their chemical properties and significantly long half-lives. Some POPs can be passed from mother to the fetus and can gain entry to the central nervous system (CNS), by crossing the blood-brain barrier (BBB), resulting in significant deleterious effects, including neurocognitive and psychiatric abnormalities, which may lead to long-term socio-economic burdens. A growing body of evidence obtained from clinical and experimental studies has increasingly indicated that these POPs may influence neurodevelopment through several cellular and molecular mechanisms. However, studies assessing their mechanisms of action are still incipient, requiring further research. Polychlorinated biphenyls (PCBs) and per- and polyfluoroalkyl substances (PFAS) are two of the main classes of POPs associated with disturbances in different human systems, mainly the nervous and endocrine systems. This narrative review discusses the main PCB and PFAS effects on the CNS, focusing on neuroinflammation and oxidative stress and their consequences for neural development and BBB integrity. Moreover, we propose which mechanisms could be involved in POP-induced neurodevelopmental defects. In this sense, we highlight potential cellular and molecular pathways by which these POPs can affect neurodevelopment and could be further explored to propose preventive therapies and formulate public health policies.