Background: The United States continues to invest considerable resources into developing the next generation of science, technology, engineering, and mathematics (STEM) talent. Efforts to shore up interest in pursuing STEM careers span decades and have increasingly focused on boosting interest among diverse student populations. Policymakers have called for engaging students in a greater STEM ecology of support that extends beyond the traditional classroom environment to increase student STEM career interest. Yet, few robust studies exist exploring the efficacy of many programmatic efforts and initiatives outside the regular curriculum intended to foster STEM interest. To maximize STEM education investments, promote wise policies, and help achieve the aim of creating STEM learning ecosystems that benefit diverse student populations and meet the nation’s STEM goals, it is crucial to examine the effectiveness of these kinds of STEM education initiatives in promoting STEM career aspirations. Purpose: The purpose of this quasi-experimental study was to examine the impact of one popular, yet understudied, STEM education initiative on students’ STEM career aspirations: participation in a university- or college-run STEM club or program activity (CPA) during high school. Specifically, we studied whether participation in a college-run STEM CPA at a postsecondary institution during high school was related to college-going students’ STEM career aspirations, and we examined whether that relationship differed depending on student characteristics and prior STEM interests. Research Design: We conducted a quasi-experimental investigation to explore the impact of participation in university- or college-run STEM CPAs on college-going students’ STEM career aspirations. We administered a retrospective cohort survey to students at 27 colleges and universities nationwide resulting in a sample of 15,847 respondents. An inverse probability of treatment weighted logistic regression model with a robust set of controls was computed to estimate the odds of expressing STEM career aspirations among those who participated in college-run STEM CPAs compared with the odds expressed among students who did not participate. Our weighting accounted for self-selection effects. Results: Quasi-experimental modeling results indicated that participation in university- or college-run STEM CPAs had a significant impact on the odds that college-going students would express STEM career aspirations relative to students who did not participate. The odds of expressing interest in a STEM career among participants in STEM CPAs were 1.49 times those of the control group. Robustness checks confirmed our results. The result held true for students whether or not they expressed interest in STEM careers prior to participation in STEM CPAs, and it held true across a diverse range of student characteristics (e.g., race, parental education, gender, standardized test scores, and family/school encouragement). Conclusions: Results suggest that university- and college-run STEM CPAs play an important role in the STEM education ecology, serving the national goal of expanding the pool of college-going students who aspire to STEM careers. Moreover, results showed that participation in university- and college-run STEM CPAs during high school is equally effective across diverse student characteristics. Policymakers, educators, and those charged with making investment decisions in STEM education should seriously consider university- and college-run STEM CPAs as a promising vehicle to promote diverse students’ STEM career aspirations in the broader STEM learning ecosystem and as an important complement to other STEM learning environments.