Memory CD8 ⁺ T cells can be broadly divided into circulating (T _CIRCM ) and tissue-resident memory T (T _RM ) populations. Despite well-defined migratory and transcriptional differences, the phenotypic and functional delineation of T _CIRCM and T _RM cells, particularly across tissues, remains elusive. Here, we utilized an antibody screening platform and machine learning prediction pipeline (InfinityFlow) to profile >200 proteins in T _CIRCM and T _RM cells in solid organs and barrier locations. High-dimensional analyses revealed unappreciated heterogeneity within T _CIRCM and T _RM cell lineages across nine different organs after either local or systemic murine infection models. Additionally, we demonstrated the relative effectiveness of strategies allowing for the selective ablation of T _CIRCM or T _RM populations across organs and identified CD55, KLRG1, CXCR6, and CD38 as stable markers for characterizing memory T cell function during inflammation. Together, these data and analytical framework provide an in-depth resource for memory T cell classification in both steady-state and inflammatory conditions.