Background. Malaria is a leading cause of morbidity and mortality in Uganda. In April 2018, malaria cases surged in Nwoya District, Northern Uganda, exceeding expected limits and thereby requiring epidemic response. We investigated this outbreak to estimate its magnitude, identify exposure factors for transmission, and recommend evidence-based control measures. Methods. We defined a malaria case as onset of fever in a resident of Anaka subcounty, Koch Goma subcounty, and Nwoya Town Council, Nwoya District, with a positive rapid diagnostic test or microscopy for malaria from 1 February to 25 May 2018. We reviewed medical records in all health facilities of affected subcounties to find cases. In a case-control study, we compared exposure factors between case-persons and asymptomatic controls matched by age and village. We also conducted entomological assessments on vector density and behavior. Results. We identified 3,879 case-persons (attack rate [AR] = 6.5%) and two deaths (case-fatality rate = 5.2/10,000). Females (AR = 8.1%) were more affected than males (AR = 4.7%) (p<0.0001). Of all age groups, 5–18 years (AR = 8.4%) were most affected. Heavy rain started in early March 2018, and a propagated outbreak followed in the first week of April 2018. In the case-control study, 55% (59/107) of case-persons and 18% (19/107) of controls had stagnant water around households for several days following rainfall (ORM-H = 5.6, 95% CI = 3.0–11); 25% (27/107) of case-persons and 51% (55/107) of controls wore full extremity covering clothes during evening hours (ORM-H = 0.30, 95% CI = 0.20–0.60); 71% (76/107) of case-persons and 85% (91/107) of controls slept under a long-lasting insecticide-treated net (LLIN) 14 days before symptom onset (ORM-H = 0.43, 95% CI = 0.22–0.85); 37% (40/107) of case-persons and 52% (56/107) of controls had access to at least one LLIN per 2 household members (ORM-H = 0.54, 95% CI = 0.30–0.97). Entomological assessment indicated active breeding sites in the entire study area; Anopheles gambiae sensu lato species were the predominant vector. Conclusion. Increased vector-breeding sites after heavy rainfall and inadequate malaria preventive measures were found to have contributed to this outbreak. We recommended increasing coverage for LLINs and larviciding breeding sites in the area.