Malaria, caused by Plasmodium falciparum (Pf), remains a leading cause of morbidity and mortality globally. Despite strong evidence for a critical role for CD8+ T cells in protective immunity, and the importance of the liver-stage as a target, the specific mechanisms by which CD8+ T cells target particularly Plasmodium-infected liver cells remain unclear, particularly in humans. To address this, we investigated the activation and effector functions of human Pf sporozoite (SPZ)-specific memory CD8+ T cells. Using an in vitroantigen-presenting cell (APC) co-culture model, we demonstrated that repeated stimulation with Pf SPZ induced the differentiation of highly activated effector-memory (Tem) CD8+ T cells expressing CD137, IFN-γ, and perforin. T cell receptor (TCR) sequencing of the activated CD137+Pf SPZ memory T cell population revealed distinct TCR clusters, suggesting clonal expansion of several Pfepitope-specific T-cells. Additionally, when stimulated with several well-known liver-stage specific epitopes, including circumsporozoite protein (CSP), thrombospondin-related anonymous protein (TRAP), and liver-stage antigen-1 (LSA-1), only circumsporozoite protein-related antigen precursor (CRA) epitope GLLGNVSTV elicited significant activation of Pf SPZ memory CD8+ T cells. This epitope induces upregulation of key activation markers (CD137, IFN-γ) and cytotoxic molecules (perforin, Granzyme A and Granzyme B), evidencing strong recognition by Pf SPZ memory T cells. This study advances our understanding of human Pf SPZ memory CD8+ T cell responses and provides a novel approach for dissecting antigen specificity and memory development which would inform the design of more effective malaria vaccines.