Methyl tert-butyl ether (MTBE), a gasoline oxygenate, is a persistent contaminant of coastal and marine environments. Given its environmental persistence, MTBE discharged into coastal waters decades ago may still pose a residual contamination risk. Despite this environmental persistence, the developmental neurotoxicity of MTBE remains poorly characterized. Here, we show that chronic exposure to MTBE beginning during embryonic development disrupts neuronal homeostasis and induces long-lasting alterations in dopaminergic neurons and behavior. In primary neuronal cultures, MTBE suppresses neuronal proliferation, increases apoptotic cell death, and impairs neurite outgrowth, indicating direct neurodevelopmental toxicity. In vivo, MTBE exposure results in a reduction of tyrosine hydroxylase–positive dopaminergic neurons, with preferential vulnerability in the ventral tegmental area. Notably, MTBE exposure is associated with increased amyloid precursor protein/β-amyloid–related pathology, suggesting involvement of molecular pathways linked to neurodegeneration. MTBE-exposed mice exhibit consistent motor impairments across multiple behavioral paradigms. Together, this study identifies MTBE as a developmental neurotoxicant that selectively compromises dopaminergic systems and establishes long-term neurological vulnerability, providing a potential link between environmental exposure and neurodegeneration-related processes.