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We explored early childhood and elementary pre-service teachers’ science and mathematics teaching efficacy with the aim to elucidate pathways to improve teacher preparation programs in this mixed methods study. Data were collected from 180 pre-service teachers from four universities in the United States. Two-level ANCOVA and regression, and a modified grounded theory analysis suggested that pre-service teachers with non-science and -mathematics majors perceived limited confidence in teaching those subjects. Pre-service teachers might benefit from science and mathematics content and pedagogical courses that were directly applicable to future teaching. The number of science and mathematics courses was associated with teaching efficacy beliefs, but not with outcome expectancy. This highlighted the importance of systematic assistance including professional development, policies, and resource supports.