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The purpose of this study was to investigate the effects of high school mathematics and science course-taking patterns on the post-secondary STEM degree attainment, when considering the various personal inputs and secondary educational contexts. This study focuses on analyzing students’ course-taking patterns in high school STEM-related subjects and how these patterns influence the likelihood of obtaining a post-secondary degree in STEM majors. The results revealed two course-taking patterns and indicate that students who followed the “advanced-level STEM” pattern were highly likely to obtain post-secondary degrees in STEM majors. This study offers insights for school leaders and teachers into efforts on student engagement and interests in the highest-level courses in mathematics and science during high school.