There are many people with chronic or severe mental disorders who are unaware that they have a diagnosable disorder or that effective treatment is available. It is plausible that this is largely because of the public’s non-alignment of biomedical understanding of mental illness which may imply lack of mental health literacy. This study investigated conceptions and attitudes toward three mental disorders, namely, depression, schizophrenia, and alcohol dependency, and beliefs about their treatment using a survey among 787 African residents of Sisonke District in the province of KwaZulu-Natal, South Africa. The results show an endorsement of multiple explanatory models of illness, thus suggesting an embracement of both Western and indigenous influences in conceptualisation of mental illness. Depression was mainly conceptualised using psychological and medical terms, and schizophrenia and alcohol dependency were conceptualised in psychological and social terms. In addition, only schizophrenia, among the three disorders investigated was conceptualised using supernatural descriptions such as bewitchment and ukuthwasa. The results of this study highlighted the strong preference among the respondents for professional help-seeking, particularly from social workers and medical practitioners, for the treatment of depression and alcohol dependency. However, traditional healing was seen as more helpful for treating schizophrenia. Regarding attitudes towards mental illness, the key findings in this study indicate that negative attitudes towards people with mental illness are widely maintained. The results of this study highlight the importance of awareness campaigns that take into consideration and respect the cultural differences of the people, collaboration between traditional and medical practitioners.