The molecular mechanisms by which signaling via transforming growth factor-β (TGF-β) and interleukin 4 (IL-4) control the differentiation of CD4⁺ IL-9-producing helper T cells (T_H9 cells) remain incompletely understood. We found here that the DNA-binding inhibitor Id3 regulated T_H9 differentiation, as deletion of Id3 increased IL-9 production from CD4⁺ T cells. Mechanistically, TGF-β1 and IL-4 downregulated Id3 expression, and this process required the kinase TAK1. A reduction in Id3 expression enhanced binding of the transcription factors E2A and GATA-3 to the Il9 promoter region, which promoted Il9 transcription. Notably, Id3-mediated control of T_H9 differentiation regulated anti-tumor immunity in an experimental melanoma-bearing model in vivo and also in human CD4⁺ T cells in vitro. Thus, our study reveals a previously unrecognized TAK1–Id3–E2A–GATA-3 pathway that regulates T_H9 differentiation.