Immunological memory is a hallmark feature of the mammalian adaptive immune response and essential for prolonged host control of pathogens. Although these features are attributed to T and B cells, previous work demonstrated that natural killer (NK) cells, which have traditionally been categorized as a component of innate immunity, also possess the ability to undergo clonal proliferation and generate memory in response to pathogens. Here we demonstrate that differentiating and ‘memory’ NK cells possess distinct chromatin accessibility profiles that are not entirely reflective of their transcriptional program, and that their epigenetic profiles reveal a ‘poised’ regulatory program at the memory stage. Additionally, among chromatin accessibility peaks that correlate with transcriptional activity throughout viral infection, proinflammatory cytokines and STATs dictate both epigenetic and transcriptional states. Finally, chromatin profiling of canonical CD8+ T cell responses against various infections allowed us to delineate accessibility signatures across naïve, effector, and memory states, and demonstrate parallel and discrete features that define NK cells and CD8+ T cells. Overall, our study reveals the dynamic nature of epigenetic imprinting during the generation of innate and adaptive lymphocyte memory.