This study examined differences between adult first-generation (AFG) and adult-continuing generation (ACG) students’ academic self-efficacy with regard to the online courses in which they were currently enrolled. The study used an online survey methodology to collect self-reported quantitative data from 1,768 undergraduate students enrolled in an online course at a mid-sized, four-year public university in the southwestern United States; 325 cases were usable for the study. The t-tests revealed no statistically significant differences between the academic self-efficacy of the AFG and ACG students. Parents’ level of educational attainment was unrelated to adult students’ academic self-efficacy with online courses. Ordinary least-squares analysis was used to evaluate student characteristics that might be associated with academic self-efficacy in the online environment. A combination of gender, GPA, age, race/ethnicity (White, Black, Hispanic, and other), and number of previous online courses predicted a statistically significant 12% of the variance in academic self-efficacy in an online environment (p < .001). Age (p < .001) and self-efficacy were positively correlated, meaning that adult students reported greater academic self-efficacy than did younger students; and number of previous online courses (p < .001) was also positively correlated to academic self-efficacy, indicating that students with greater experience with online courses reported a greater sense of academic self-efficacy in that environment than students who had completed fewer online courses. This study has implications of providing additional insight for higher education practitioners working with adult learners. Identifying additional factors influencing adult learners’ academic self-efficacy in an online academic environment may be useful when building effective strategies to improve online retention and completion rates for these students. Future research should examine a wider variety of variables beyond demographic characteristics. External and internal factors, along with existing theories of behaviors should be investigated to help explain adult persistence and retention online and in face-to-face courses.