Acute viral infections typically generate functional effector CD8+ T cells (T CD8) that aid in pathogen clearance. However, during acute viral lower respiratory infection, lung T CD8 are functionally impaired and do not optimally control viral replication. T cells also become unresponsive to Ag during chronic infections and cancer via signaling by inhibitory receptors such as programmed cell death-1 (PD-1). PD-1 also contributes to T CD8 impairment during viral lower respiratory infection, but how it regulates T CD8 impairment and the connection between this state and T cell exhaustion during chronic infections are unknown. In this study, we show that PD-1 operates in a cell-intrinsic manner to impair lung T CD8. In light of this, we compared global gene expression profiles of impaired epitope-specific lung T CD8 to functional spleen T CD8 in the same human metapneumovirus–infected mice. These two populations differentially regulate hundreds of genes, including the upregulation of numerous inhibitory receptors by lung T CD8. We then compared the gene expression of T CD8 during human metapneumovirus infection to those in acute or chronic lymphocytic choriomeningitis virus infection. We find that the immunophenotype of lung T CD8 more closely resembles T cell exhaustion late into chronic infection than do functional effector T cells arising early in acute infection. Finally, we demonstrate that trafficking to the infected lung alone is insufficient for T CD8 impairment or inhibitory receptor upregulation, but that viral Ag–induced TCR signaling is also required. Our results indicate that viral Ag in infected lungs rapidly induces an exhaustion-like state in lung T CD8 characterized by progressive functional impairment and upregulation of numerous inhibitory receptors.