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Improper disposal of waste has implications for public health worldwide. This issue is not limited to use polythene bags alone. Notably, over 53% of solid wastes are generated in urban areas, especially within households. Managing solid wastes including polythene bags, used as daily shopping bags, requires strict interventional measures. There is porosity in executing these measures. This study, therefore, assessed knowledge, attitude, and practices of disposing used polythene bags among residents of Lira City. A cross-sectional survey was employed. Quantitative data using structured questionnaires were collected among 421 randomly selected residents of Lira City. Data was analysed using STATA Version 17, summarized as frequencies, percentages, means, and standard deviations. Pearson Chi-square test was run for bivariate analysis, and multivariate analysis using logistic regression at 95% CI, and a p-value of 0.05 to obtain significant variables associated with the outcome variable. Overall, the response rate was 99.8%. Even then, more than half of the respondents had poor practices of disposal (52.5%). Yet a good number of the respondents 42.5% were aged 18 to 28 years, female 64.9%, and 34.9% attained a primary level of education. Although most of the respondents were self-employed 41.1%, married 61.3%, and Catholic 35.2%, the majority 78.9% had good knowledge of proper disposal of used polythene bags. Significantly, age [AOR = 3.007; 95% CI; 1.074–8.417], Sex [AOR = 1.2; 95% CI; 0.82–1.97], Reduced Injuries [AOR = 1.2; 95% CI; 0.38–4.15], Drainage blockage [AOR = 3.04; 95% CI; 2.00-4.63], and Human Health Problems [AOR = 1.7; 95% CI; 1.15–2.73] were associated with disposal of used polythene bags among residences in Lira City. Despite high levels of knowledge, improper disposal of used polythene bags remained common practices among urban households in Lira City, significantly influenced by age and perceived risks related to drainage blockage and human health. Targeted community education focusing on younger residents and strengthened enforcement of existing waste management bylaws are recommended.