This article reports the findings from a qualitative study to understand the provision of electronic mentoring (e-mentoring) to support the educational persistence of students with disabilities at a two-year college in a large city in the U.S. South. Building upon a five-year project at three postsecondary institutions and three secondary school systems, this article presents the results from interviews with selected participants, which were analyzed using a qualitative case study design. Three aspects of a STEM e-mentoring program were examined: (1) the use of virtual environments and social media settings; (2) the development of e-mentoring relationships; and (3) the examination of persistence constructs. Eight participants were recruited for the study representing individuals with disabilities, non-traditional age students, and individuals from minority populations. Four critical findings were observed: (1) virtual environments and social media tool usage varied depending on context, accessibility, and practical considerations; (2) STEM learning and emotional supports were enhanced when embedded in the practice of e-mentoring; and (3) five persistence constructs (intention to persist, self-determination, self-advocacy, science affect, and math affect) informed STEM outcomes for community college students with disabilities.