Long-term immunity depends partly on the establishment of memory CD8 T cells. We identified a counterregulatory network between the homologous transcription factors ZEB1 and ZEB2 and the microRNA family, which modulates effector CD8 T cell fates. Unexpectedly, and had reciprocal expression patterns and were functionally uncoupled in CD8 T cells. ZEB2 promoted terminal differentiation, whereas ZEB1 was critical for memory T cell survival and function. Interestingly, the transforming growth factor β (TGF-β) and miR-200 family members, which counterregulate the coordinated expression of and during the epithelial-to-mesenchymal transition, inversely regulated and expression in CD8 T cells. TGF-β induced and sustained expression in maturing memory CD8 T cells. Meanwhile, both TGF-β and family members selectively inhibited Additionally, the miR-200 family was necessary for optimal memory CD8 T cell formation. These data outline a previously unknown genetic pathway in CD8 T cells that controls effector and memory cell fate decisions.