Employing a comparative case study and using state effectiveness as a conceptual framework, this research explores malaria and its control in Uganda and Rwanda. These two neighbouring countries, which share a significant number of socio-economic characteristics, have been implementing the malaria control policies widely recommended by the World Health Organization (WHO). Despite their similarities, and the implementation of comparable malaria control policies, the two countries have experienced divergent outcomes: a reduction in malaria-related hospital admission and death rates in Rwanda, and an overall increase in malaria-related hospitalizations and deaths in Uganda during the same 2000-2015 period. During fieldwork in both countries over the span of several months, data was collected using key informant interviews; observation at four sites; and examination of government documents. The key findings suggest that the variation in malaria policy outcomes is due largely to political factors including the role of political leaders and institutions (i.e. the Presidency, the ruling party and parliament), and not to technical factors, as most of the literature suggests. The politicization of malaria and its control in Rwanda (i.e. putting responsibility for malaria control in the hands of political leaders), and the de-politicization of malaria control in Uganda explains the divergence in malaria control outcomes.