The purpose of this study was to investigate the effectiveness of virtual mentoring for enhancing the persistence of secondary and postsecondary students with disabilities engaged in science, technology, engineering, and mathematics (STEM) learning. The student participants (N = 189) were all engaged in STEM coursework and enrolled in a virtual-mentoring program for a span of 4 years. Persistence was measured with an online survey designed to evaluate growth across self-determination, self-advocacy, STEM aspirations, and self-efficacy (math and science). After participating in virtual-mentoring practices, the most significant improvement was demonstrated in students' perception of self-determination and self-advocacy. Growth differences were identified across type of disability and race/ethnicity populations. Implications pertaining to STEM aspirations and self-efficacy were addressed.