The vertebrate adaptive immune system has well defined functions in maintaining tolerance to self‐tissues. Suppression of autoreactive T cells is dependent on the regulatory cytokine transforming growth factor‐β (TGF‐β) and regulatory T (Treg) cells, a distinct T cell lineage specified by the transcription factor Foxp3. Although TGF‐β promotes thymic Treg (tTreg) cell development by repressing T cell clonal deletion and peripheral Treg cell differentiation by inducing Foxp3 expression, a recent study shows that TGF‐β suppresses autoreactive T cells independent of Foxp3+ Treg cells. These findings imply that as an ancestral growth factor family member, TGF‐β may have been co‐opted as a T cell‐intrinsic mechanism of self‐tolerance control to assist the evolutionary transition of vertebrate adaptive immunity. Later, perhaps in placental mammals upon their acquisition of a TGF‐β regulatory element in the Foxp3 locus, the TGF‐β pathway is further engaged to induce peripheral Treg cell differentiation and expand the scope of T cell tolerance control to innocuous foreign antigens. In ancestral vertebrates, TGF‐β signaling might be co‐opted to suppress autoreactive T cells (Taut). In non‐Eutherian jawed vertebrates, TGF‐β further supports thymic Treg cells (tTreg) development to repress Taut. In Eutherians, TGF‐β induces peripheral Treg cells (pTreg) differentiation to suppress allogenic T cells (Tallo) and commensal‐reactive T cells (Tcom).