Abstract Multiple Sclerosis (MS) is an autoimmune disease that affects more than one million people in the United States and is characterized by the demyelination of axons in the central nervous system (CNS). While the etiology of the MS is unknown, CD4 T cells are central to disease pathogenesis. The transcription factor STAT4 is critical for Th1 cell development, is associated with risk for MS, and is required for experimental autoimmune encephalomyelitis (EAE), an animal model of MS. Interestingly, we and others find that many Th1 associated molecules such as IL-12, IFNγ and Tbet are dispensable for EAE. Hence, we hypothesize that STAT4 functions in effector CD4 T cells to promote neuroinflammation independent of the classical Th1 pathway. To test the potential role of STAT4 in Th17 cells, we employed the adoptive transfer model EAE. While we note that STAT4 expression does not impact the development of Th17 cells, it is required for the migration of Th17 cells into the CNS and for Th17 mediated demyelination. Moreover, RNA sequencing analysis shows that STAT4 regulates the expression of >200 genes in the Th17 cells, many of which skew the balance between regulatory and inflammatory Th17 cell function such as Il10 and Tbx21, respectively. Together, these data reveal a novel role of STAT4 in controlling the functional properties of Th17 cells, and this may provide a promising therapeutic target for patients affected by Th17 driven autoimmune diseases.