Streptococcus pyogenes is a globally ubiquitous bacterium often associated with mild, self-limiting cases of “strep throat”, or pharyngitis, in young children. However, it is also responsible for lesser-known pathogeneses like invasive skin infections and acute rheumatic fever, both of which disproportionately afflict First Nations Australians and low- and middle-income countries. There is an urgent need to develop an effective vaccine against S. pyogenes, yet our limited understanding of how infection-induced cellular and antibody-mediated immune memory develop and contribute to protection against infection remains a hurdle for vaccine development. Here, we combine antigen tetramers and activation-induced marker (AIM) assays to phenotypically profile S. pyogenes antigen-specific B and T cell responses, respectively, in blood from healthy adults (n=25) before and after experimental pharyngeal challenge of emm75 S. pyogenes. Memory B and CD4+ T cells specific to all antigens (n=4-6) were detectable before challenge in most participants. In participants who developed symptomatic pharyngitis, antigen-specific memory T and B cells significantly expanded at one week post challenge and, in some cases, remained elevated for at least three months. Infection also induced a transient burst of antibody-secreting cells and elicited a CD4+ T cell response dominated by regulatory T cells, Th17, and Th17.1 subsets. Pre-existing B cell memory to some antigens was associated with milder clinical symptoms, and more severe infection correlated with some stronger T and B cell responses. Together, our findings demonstrate that human infection generates immune memory to key vaccine candidate antigens and reveal how a single exposure shapes S. pyogenes humoral and cellular immunity.