IMPORTANCE: Research on the factors contributing to low academic performance of first-generation students studying occupational therapy is limited, and how these factors affect the students' academic performance is insufficiently described. OBJECTIVE: To explore how first-generation students in occupational therapy perceive their academic self-efficacy, academic engagement, and social integration. DESIGN: Explanatory sequential mixed-methods design. SETTING: Occupational therapy program on the East Coast of the United States. PARTICIPANTS: The total sample included 18 first-generation students in occupational therapy through purposeful sampling. Eighteen participants completed the survey, and 5 participants participated in the interview. OUTCOMES AND MEASURES: Measures included a demographic questionnaire, the Self-Efficacy for Learning Form-Abridged, the Survey of Student Engagement, the Social Integration Scale, and semistructured interviews. RESULTS: Participants reported a low level of academic self-efficacy, academic engagement, and social integration. CONCLUSIONS AND RELEVANCE: This study fills the gap in research regarding factors contributing to low academic performance of first-generation students in occupational therapy and how the identified barriers of academic self-efficacy, academic engagement, and social integration can be addressed for these students. Plain-Language Summary: This study explored how first-generation occupational therapy students think about their academic performance, engagement, and social integration. Students reported a low level of academic performance, engagement, and social integration. Identifying and understanding the factors that affect the academic performance of first-generation students can improve the support and services provided by occupational therapy programs to first-generation students. Positionality Statement: Positionality is described as the location of the researcher in their research (Milner, 2007). It influences the researcher's assumptions, findings, and interpretations (Banks, 2015). As a first-generation doctoral student, I identify with the unique challenges faced by many first-generation students. As Milner (2007) suggested, it is important to be introspective during research and acknowledge any internal biases to maintain objectivity during the research process. I aimed to be reflexive by taking notes about my thoughts throughout the study to actively reflect on my understanding of how my positionality may affect my data collection and analysis.