The study explores lay conceptualizations of mental illness among the Akans of Ghana as influenced by their cultural worldview. Akan, the largest ethnic group in Ghana, is noted for the use of supernatural attributions for various health-related issues. The supernatural attributions are based on Akan ontological belief that the universe is unitary such that there is no clear distinction between physical and spiritual occurrences. This worldview guides Akans in how they deal with a wide range of issues including their mental health. Clinicians and other mental health professionals who rely solely on biomedical approaches to mental health fail to meet the demands of Akan mental health help-seekers because such approaches do not recognize the cultural factors that inform lay understandings on mental illness. Limited studies have been conducted on how Akan supernatural attributions influence conceptualizations of mental illness. Using a grounded theory method of research, 14 individual interviews and 7 focus group interviews were conducted to explore beliefs and knowledge about mental illness in two indigenous Akan communities in Ghana. Participants were of diverse age, sex, education, and occupational background. Analysis revealed that cultural factors influence lay conceptions, diagnosis, and treatment of mental illness. Local labels for mental illness as well as beliefs about etiology, development, and cure of mental illness were identified. It was found that the Akan unitary worldview aids in the endorsement of heterogeneous multi-tier causal attributions of mental illness that embrace supernatural and non-supernatural causal explanations. Although supernatural causality theories of mental illness existed, participants related a complex causal explanation that involved other non-supernatural causal attributions. Results further revealed that Akan cultural beliefs influence community response to mental illness, encouraging pluralistic help-seeking behaviors that satisfy the Akan cultural value for holistic treatment and care. The implications of the findings for clinical training, culturally-sensitive mental health practice, and mental health education and advocacy have been discussed.