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Shortages of science and mathematics teachers are a concern in the US. Despite the implementation of intervention strategies to address this problem at the high school level, little empirical research had been conducted to inform these initiatives. This retrospective cohort study used multinomial logistic regression models to predict students’ science and mathematics teaching career intentions at the end of high school. These intentions were strongly associated with having had an interest in science and mathematics teaching already at the beginning of high school. Strong mathematics preparedness and a desire to help others also predicted science and mathematics teaching career intentions. This research highlights experiences that may identify prospective teachers and offers recommendations for the content of high school level interventions.