This study investigated the causes of homelessness in Ghana and associated psychosocial distress. A sample of 86 homeless participants listed perceived causes of their homelessness and completed measures of psychosocial distress, and 97 non-homeless participants completed the same measures psychosocial distress. Causes of homelessness among the participants included poverty (30.1%), migration (10.4%), unemployment (2.2%), parental demise (2.2%), parental neglect (0.5%), and parental divorce (0.5%). Multivariate analysis revealed higher psychosocial distress among the homeless than the non-homeless. Homeless females reported higher levels of stress and suicidality than their male counterparts. The study demonstrates the need for timely and effective implementation of interventions such as provision of affordable housing, financial assistance, job-creation, and skill training for the homeless directly related to known causes of homelessness and accounting for gender differences.