CMV remains an important opportunistic pathogen in solid organ transplantation, particularly in lung transplant recipients (LTRs). LTRs mismatched for CMV (donor+/recipient−; D+ R−) are at high-risk for active CMV infection and increased mortality, however the immune correlates of viral control remain incompletely understood. We prospectively studied 23 D+ R− LTRs during primary CMV infection to determine whether acute CD8+ T cell parameters differentiated the capacity for viral control in early chronic infection. T-box transcription factors expression patterns of T-bet> Eomesodermin (Eomes) differentiated LTR controllers from viremic relapsers and reciprocally correlated with granzyme B loading, and CMV phosphoprotein 65 (pp65)–specific CD8+ IFN-γ+ and CD107a+ frequencies. LTR relapsers demonstrated reduced CD8+ Ki67+ cells ex vivo and substantially impaired CD8+ pp65-specific in vitro proliferative responses at 6 d, with concomitantly lower pp65-specific CD4+ IL-2+ frequencies, as compared with LTR controllers. However, CMV-specific in vitro proliferative responses could be significantly rescued, most effectively with pp65 Ag and exogenous IL-2, resulting in an increased T-bet: Eomes balance, and enhanced effector function. Using class I CMV tetramers, we observed similar frequencies between relapsers and controllers, although reduced T-bet: Eomes balance in tetramer+ cells from relapsers, along with impaired CD8+ effector responses to tetramer-peptide restimulation. Taken together, these data show impaired CMV-specific CD8+ effector responses is not for complete lack of CMV-specific cells but rather underscores the importance of the T-bet: Eomes balance, with CMV-specific proliferation a key factor driving early T-bet expression and effector function in CD8+ T cells during primary infection and differentiating the capacity of high-risk LTRs to establish immune control during early chronic infection.