Interleukin-17 (IL-17)-secreting T cells of the T helper 17 (T H 17) lineage play a pathogenic role in multiple inflammatory and autoimmune conditions and thus represent a highly attractive target for therapeutic intervention. We report that inhibition of acetyl-CoA carboxylase 1 (ACC1) restrains the formation of human and mouse T H 17 cells and promotes the development of anti-inflammatory Foxp3+ regulatory T (T reg ) cells. We show that T H 17 cells, but not T reg cells, depend on ACC1-mediated de novo fatty acid synthesis and the underlying glycolytic-lipogenic metabolic pathway for their development. Although T H 17 cells use this pathway to produce phospholipids for cellular membranes, T reg cells readily take up exogenous fatty acids for this purpose. Notably, pharmacologic inhibition or T cell–specific deletion of ACC1 not only blocks de novo fatty acid synthesis but also interferes with the metabolic flux of glucose-derived carbon via glycolysis and the tricarboxylic acid cycle. In vivo, treatment with the ACC-specific inhibitor soraphen A or T cell–specific deletion of ACC1 in mice attenuates T H 17 cell–mediated autoimmune disease. Our results indicate fundamental differences between T H 17 cells and T reg cells regarding their dependency on ACC1-mediated de novo fatty acid synthesis, which might be exploited as a new strategy for metabolic immune modulation of T H 17 cell–mediated inflammatory diseases.