CD8+ tissue-resident memory T cells (T RM cells) are poised at the portals of infection and provide long-term protective immunity. Despite their critical roles, the precise mechanics governing T RM cell reactivation in situ are unknown. Using a TCR-transgenic Nur77-GFP reporter to distinguish “antigen-specific” from “bystander” reactivation, we demonstrate that lung CD8+ T RM cells are reactivated more quickly, yet less efficiently, than their counterparts in the draining LNs (T LN cells). Global profiling of reactivated memory T cells revealed tissue-defined and temporally regulated recall response programs. Unlike the reactivation of CD8+ T LN cells, which is strictly dependent on CD11c+ XCR1+ APCs, numerous antigen-presenting partners, both hematopoietic and non-hematopoietic, were sufficient to reactivate lung CD8+ T RM cells, but the quality of T RM cell functional responses depended on the identity of the APCs. Together, this work uncovers fundamental differences in the activation kinetics, mechanics, and effector responses between CD8+ memory T cells in peripheral vs. lymphoid organs, revealing a novel tissue-specific paradigm for the reactivation of memory CD8+ T cells.