Despite efforts to avert the negative effects of malaria, there remain barriers to the uptake of prevention measures, hindering its eradication. This qualitative case study explored factors influencing uptake of malaria prevention strategies among pregnant women and children under-five years and the impact of COVID-19 in a malaria endemic rural district in Uganda. The study found that although pregnant women and caregivers of children under-five years recognized symptoms of malaria infection, healthcare-seeking was not apt as some respondents used alternative approaches and delayed seeking formal healthcare. It is imperative to focus on the promotion of malaria prevention strategies and address drawbacks associated with misconceptions about these interventions, and promotion of health-seeking behaviors. As COVID-19 exacerbated the effect of malaria prevention uptake and healthcare seeking, it’s critical to recommit and integrate COVID-19 prevention measures in normative living and restrict future barriers to healthcare access.