Oligodendroglia support axon survival and function through mechanisms independent of myelination, and their dysfunction leads to axon degeneration in several diseases. The cause of this degeneration has not been fully determined, but a lack of energy metabolites such as glucose or lactate has been hypothesized. Lactate is transported exclusively by monocarboxylate transporters (MCTs), and changes in these transporters can alter lactate production and utilization. This study shows that MCT1, the most abundant lactate transporter in the central nervous system (CNS), is highly enriched within oligodendroglia. Disruption of this transporter produces axon damage and neuron loss in animal and cell culture models. Additionally, MCT1 expression is reduced in patients with amyotrophic lateral sclerosis (ALS) and mouse models of the disease, suggesting a role for oligodendroglial MCT1 in pathogenesis. The findings define a new fundamental mechanism by which oligodendroglia support neurons and axons.Oligodendroglia support axon survival and function through mechanisms independent of myelination, and their dysfunction leads to axon degeneration in several diseases. The cause of this degeneration has not been fully determined, but a lack of energy metabolites such as glucose or lactate has been hypothesized. Lactate is transported exclusively by monocarboxylate transporters (MCTs), and changes in these transporters can alter lactate production and utilization. This study shows that MCT1, the most abundant lactate transporter in the central nervous system (CNS), is highly enriched within oligodendroglia. Disruption of this transporter produces axon damage and neuron loss in animal and cell culture models. Additionally, MCT1 expression is reduced in patients with amyotrophic lateral sclerosis (ALS) and mouse models of the disease, suggesting a role for oligodendroglial MCT1 in pathogenesis. The findings define a new fundamental mechanism by which oligodendroglia support neurons and axons.