A fundamental function of CD4⁺ helper T (T_H) cells is the regulation of B cell–mediated humoral immunity. Development of T follicular helper (T_FH) cells that provide help to B cells is mediated by the cytokines interleukin-6 and interleukin-21 but is independent of T_H1, T_H2, and T_H17 effector cell lineages. Here, we characterize the function of Bcl6, a transcription factor selectively expressed in T_FH cells. Bcl6 expression is regulated by interleukin-6 and interleukin-21. Bcl6 overexpression induced T_FH-related gene expression and inhibited other T_H lineage cell differentiation in a DNA binding–dependent manner. Moreover, Bcl6 deficiency in T cells resulted in impaired T_FH cell development and germinal center reactions, and altered production of other effector T cell subsets. Our data thus illustrate that Bcl6 is required for programming of T_FH cell generation.