Understanding the developmental mechanisms of follicular helper T cells (T_FH cells) in humans is relevant to the clinic. However, the factors that drive the differentiation of human CD4⁺ helper T cells into T_FH cells remain largely undefined. Here we found that transforming growth factor-β (TGF-β) provided critical additional signals for the transcription factors STAT3 and STAT4 to promote initial T_FH differentiation in humans. This mechanism did not appear to be shared by mouse helper T cells. Developing human T_FH cells that expressed the transcriptional repressor Bcl-6 also expressed RORγt, a transcription factor typically expressed by the T_H17 subset of helper T cells. Our study documents a mechanism by which T_FH cells and T_H17 cells emerge together in inflammatory environments in humans, as is often observed in many human autoimmune diseases.