Negative regulatory processes, such as anergy and exhaustion, cause active suppression of CD8+ T cell effector functions. A longstanding question has been to what extent the same molecular pathways control exhaustion and anergy. We have addressed this question by examining the role of a transcriptional master regulator of anergy, EGR2, within the CD8+ T cell exhaustion process. We demonstrate that EGR2 expression is elevated in an antigen-dependent manner within exhausted cells relative to functional effectors in the LCMV model of exhaustion. EGR2 loss triggered a block in terminal exhaustion, with evidence of direct EGR2-dependent regulation of key genes such as Pdcd1, Tigit, Bcl6, Bach2 and Tcf7. Strikingly, the suite of genes directly regulated by EGR2 in the context of exhaustion minimally overlapped with previously characterized direct targets of EGR2 during anergy. Collectively, these data suggest that exhausted cells “re-purpose” a TCR-induced, anergy-associated transcription factor to promote terminal exhaustion.