Mental health disorders account for a heavy disease burden in Uganda. In order to provide culturally appropriate mental health prevention and treatment approaches, it is necessary to understand how mental health is conceptualized in the population. Three focus group discussions (FGDs) and 31 in-depth interviews (IDIs) were conducted with men and women aged 14 to 62 years residing in rural, urban, and semi-urban low-income communities in central and western Uganda to explore perceptions and knowledge of mental health. Interpretive thematic analysis was undertaken; results were organized through the lens of the mental health literacy framework. Environmental and societal stressors were identified as primary underlying causes of poor mental health. While participants recognized symptoms of poor mental health, gaps in mental health literacy also emerged. Mental health resources are needed in this setting and additional qualitative work assessing knowledge and attitudes toward mental health care seeking behavior can inform the development of acceptable integrated services.