Interleukin-23 (IL-23) is required for inflammatory Th17 cell function in experimental autoimmune encephalomyelitis (EAE), and IL-23 blockade reduces the number of effector Th17 cells in the CNS. We report that pro-inflammatory Th17 cells express high integrin β₃ that is IL-23 dependent. Integrin β₃ was not upregulated on all activated T cells; rather, integrin β₃ was upregulated along with its functional partner integrin α_v on effector Th17 cells and "ex-Th17" cells, and α_vβ₃^hi RORγt⁺ cells expanded during EAE. Integrin α_vβ₃ inhibitors ameliorated clinical signs of EAE, and integrin β₃ deficiency on CD4⁺ T cells alone was sufficient to block EAE induction. Furthermore, integrin-β₃-deficient Th17 cells, but not Th1 cells, were impaired in their ability to induce EAE. Integrin β₃^−/− T cells induced smaller demyelinated lesions and showed reduced spread and accumulation within the CNS, corresponding with impaired extracellular-matrix-mediated migration. Hence, integrin β₃ is required for Th17 cell-mediated autoimmune CNS inflammation.