CD4+ T follicular helper cells (T FH) are critical for the formation and function of B cell responses to infection or immunization, but also play an important role in autoimmunity. The factors that contribute to the differentiation of this helper cell subset are incompletely understood, although several cytokines including IL-6, IL-21, and IL-12 can promote T FH cell formation. Yet, none of these factors, nor their downstream cognate STATs, have emerged as nonredundant, essential drivers of T FH cells. This suggests a model in which multiple factors can contribute to the phenotypic characteristics of T FH cells. Because type I IFNs are often generated in immune responses, we set out to investigate whether these factors are relevant to T FH cell differentiation. Type I IFNs promote Th1 responses, thus one possibility was these factors antagonized T FH-expressed genes. However, we show that type I IFNs (IFN-α/β) induced B cell lymphoma 6 (Bcl6) expression, the master regulator transcription factor for T FH cells, and CXCR5 and programmed cell death-1 (encoded by Pdcd1), key surface molecules expressed by T FH cells. In contrast, type I IFNs failed to induce IL-21, the signature cytokine for T FH cells. The induction of Bcl6 was regulated directly by STAT1, which bound to the Bcl6, Cxcr5, and Pdcd1 loci. These data suggest that type I IFNs (IFN-α/β) and STAT1 can contribute to some features of T FH cells but are inadequate in inducing complete programming of this subset.