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Student achievement is an important aspect for college aspiration and future career choices. Students with higher self-efficacy tend to have a stronger motivation, higher achievement, and greater ambitions. As self-efficacy and student achievement have a powerful relationship, factors that mediate this relationship become highly important as well. This study investigated whether high school students’ mathematics interest mediate the relationship between mathematics self-efficacy and students’ reasons for taking mathematics courses. This descriptive causal comparative study used publicly available data from the 2009 High School Longitudinal Study; data was analyzed through Hierarchical Regression analyses; mediation testing was conducted using Andrew Hayes’ PROCESS software. Findings revealed that students’ mathematics interest moderately mediated the relationship between self-efficacy and reasons for mathematics course selection.