Background <p>Caring for individuals with mental illness is stressful, with challenges like stigma, unequal responsibilities, and patient behavior. These stressors impact caregivers’ mental health and treatment outcomes, yet little is known about coping strategies in Ethiopia. Therefore, this mixed-methods study assessed the coping strategies, lived experiences, and determinants for coping among family caregivers of patients with mental illness in northwest Ethiopia.</p> Methods <p>A convergent parallel mixed-methods study was conducted between June and July 2024. A total of 592 caregivers were selected using systematic random sampling. Data were collected through face-to-face interviews. Coping strategies were assessed using the 28-item Brief-COPE tool, while qualitative data were collected via tape-recorded in-depth interviews. Quantitative data were analyzed with SPSS AMOS Version 23 software using structural equation modeling, and qualitative data were analyzed with inductive thematic analysis using NVivo-15.</p> Results <p>The mean adaptive and maladaptive coping scores were 34.65 (SD = 7.70) and 21.10 (SD = 5.00), respectively. Lower adaptive coping was significantly associated with being a farmer (β = -0.21), female sex (β = -0.10), older age (β = -0.07), longer illness duration (β = -0.10), and a higher number of patient hospital admissions (β = -0.07). Experiences of physical abuse and repeated hospitalizations also indirectly reduced adaptive coping. In contrast, perceived stigma showed a small but positive association with adaptive coping. Higher maladaptive coping was strongly predicted by caregiving burden (β = 0.39) and psychological distress (β = 0.13), with additional indirect effects from comorbid illnesses and abuse experiences. Social support demonstrated a protective effect by indirectly reducing maladaptive coping. Overall, family caregivers experienced substantial emotional, financial, and social challenges, underscoring the need for interventions that reduce caregiver burden, enhance social support, and address psychological distress.</p> Conclusion <p>Family caregivers exhibited lower coping strategies compared with the general population, highlighting their vulnerability. The findings indicate that caregiving burden and psychological distress play a central role in maladaptive coping, while social support serves as a protective factor. These results emphasize the need for comprehensive caregiver-focused interventions and the integration of caregiver support into mental health policies to promote adaptive coping and sustainable caregiving.</p>