Thyroid hormones (TH) are critical regulators of neurogliogenesis, neural stem cell fate specification, oligodendrocyte differentiation and myelination during the perinatal period. Disruption of TH signaling during this sensitive developmental window may induce long-lasting alterations in adult neurogenesis and myelin development and repair, increasing vulnerability to demyelinating disorders. We investigated whether perinatal exposure to per- and polyfluoroalkyl substances (PFAS), known endocrine disruptors of TH homeostasis, produces persistent functional consequences on neurogliogenesis and myelin integrity. Using complementary in vivo and ex vivo models, we show that perfluorooctane sulfonate (PFOS), but not perfluorooctanoic acid (PFOA), alters both neurogenesis and oligodendrogenesis and impairs functional remyelination. In Xenopus laevis Tg(mbp:GFP-NTR), PFOS exposure inhibited spontaneous remyelination and altered visually guided behavior. In lysolecithin-demyelinated mouse cerebellar slices, PFOS reduced remyelination, an effect rescued by TH supplementation, supporting the involvement of altered TH signaling. In mice, maternal PFOS exposure during late gestation and lactation led to PFOS accumulation within offspring myelin and induced long-term alterations in subventricular zone (SVZ) neurogliogenesis. PFOS transiently shifted neural stem cell lineage specification toward oligodendrogenesis at the expense of neurogenesis during early postnatal stages, while impairing oligodendrocyte precursor cell maturation in adulthood. PFOS exposure was also associated with reduced numbers of adult-born dopaminergic interneurons in the olfactory bulb and altered olfactory memory in adult offspring. Ultrastructural analyses further revealed sustained thinning and disorganization of the myelin sheath. In vitro, PFAS altered the biophysical properties of myelin lipid membranes, indicating combined indirect endocrine and direct membrane effects.