Solid waste management has become the greatest public health problem facing many urban and semi-urban areas in Ghana. Great wealth can be generated from wastes if managed effectively but also has high probability of causing serious health and environmental problems if not effectively managed. The study sought to determine factors militating against domestic solid waste management in Hohoe, possible ways of curbing them and also to assess the methods of domestic solid waste management. This study used descriptive cross-sectional survey and structured questionnaire to obtain the required information from respondents. A total number of 403 respondents were recruited into the study. The data collected were entered and analyzed using Statistical Package for Social Sciences version 20. The relationships between socio-demographic characteristics of the respondents and their use or non-use of apt domestic solid waste disposal methods were examined using chi-square analysis. The study found that 44% of respondents disposed domestic waste into central skip over dustbins. Spilled over of skip over dustbin has caused 8% of respondents to practice open burning. 7% dumped on undeveloped building plots, 5% dumped elsewhere, and 3% dumped into the river course. About 78% of respondents reported that mobilization of cleanups was irregular. The result from the study also showed a statistical significant association between practice of domestic solid waste management and religion [χ 2 (2, 403) = 60.9484, p < 0.001, α = 5%]. About 96% of Christians practiced good methods of domestic solid waste management compared to 4% of Muslims. The findings painted a gloomy picture of poor domestic solid waste management practice among the respondents in the study communities.