Broad political knowledge better equips citizens to discharge the responsibilities of good citizenship, such as monitoring local government programs. Empirical studies show a connection between citizens’ political knowledge and their participation in monitoring activities in contexts other than a decentralized local government system in a developing country. Thus, in this paper, we set out to provide new empirical evidence by assessing the link between citizens’ political knowledge and their participation in monitoring local government programs in Buliisa and Kampala districts of Uganda. We employed a convergent parallel research design. We gathered data using survey questionnaire, key informant interviews, and focus group discussions. We analyzed quantitative data using STATA and performed thematic analysis for the qualitative data. Generally, results showed that the level of political participation of citizens in monitoring local government programs was significantly and positively associated with their level of knowledge of local political affairs. This was especially marked in Kampala compared to Buliisa district. Conclusively, the nature of the association between the aforesaid variables could differ depending on the form of local political knowledge and/or the nature of political participation being measured.