CD8⁺ T lymphocytes are required for effective host defense against pathogens and also for mediating effector responses against uncontrolled proliferating self‐tissues. In this study, we determine that individual CD8⁺ T cells are tightly controlled in their effector functions by CD152 (CTLA‐4). We demonstrate that signals induced by CD152 reduce the frequency of IFN‐γ and granzyme B expressing CD8⁺ T cells independently of the transcription factors T‐bet or cKrox by selectively inhibiting accumulation of Eomesodermin mRNA and protein. Ectopic expression of Eomesodermin reversed the CD152‐mediated inhibition of effector molecule production. Additionally, enhanced cytotoxicity of individual CD8⁺ T cells differentiated in the absence of CD152 signaling was determined in vivo. These novel insights extend our understanding of how immune responses of CD8⁺ T cells are selectively modulated.