Over the past decade, CTE has been highlighted as a means of promoting college and career readiness for high school students. Applied STEM coursework is a promising area of high school study that has particular relevance in the technologically progressive world of today. Previous research has illustrated that applied STEM coursework in high school is associated with a number of positive educational outcomes. Importantly, no previous empirical investigation has examined the relationship between applied STEM coursework and students' reported levels of math and science self-efficacy, two important harbingers of academic ability and success. Consequently, the current study used nationally representative data to explore applied STEM coursework participation and self-efficacy. Results indicated that applied STEM coursework was predictive of increases in both math and science self-efficacy, except among females and students with disabilities (SWDs). Implications for policy are discussed.