Levels of anti‐inflammatory extracellular adenosine are controlled by the sequential action of the ectonucleotidases CD39 and CD73, whose expression in CD4⁺ T cells has been associated with natural regulatory T cells (nTregs). We here show that CD73 expression on activated murine CD4⁺ T cells is induced by TGF‐β independently of Foxp3 expression, operates at the transcriptional level and translates into gain of functional capacity to generate adenosine. In the presence of AMP, CD73 induced by TGF‐β generates adenosine able to suppress proliferation of activated CD4⁺ T cells in vitro. These effects are contextual and opposed by proinflammatory cytokines. CD73 is also upregulated by TGF‐β in CD8⁺ T cells, DCs and macrophages, so providing an amplification mechanism for adenosine generation in tissue microenvironments. Together, these findings expose a novel anti‐inflammatory role for TGF‐β.