Resident memory T cells (T_RM) provide localized protection due to their position in barrier tissues. However, interstitial signals necessary for their formation and persistence are not properly understood. This study demonstrated that antigen-dependent induction of the chemokine receptor, CXCR6, is a conserved requirement for T_RM formation in peripheral tissue after viral infection. Cutaneous murine viral infection was used to define the kinetics of CXCR6 expression and its impact on the transition of effector CD8⁺ T cells to long-term tissue residence. This dataset includes single cell RNA sequencing data. The results indicate that CXCR6 initiates mechanisms of cellular adaptation to tissue and promotes local survival.