As countries of sub-Saharan Africa expand irrigation to improve food security and foster economic growth, it is important to quantify the malaria risk associated with this process. Irrigated ecosystems can be associated with increased malaria risk, but this relationship is not fully understood. We studied this relationship at the Bwanje Valley Irrigation Scheme (800 hectares) in Malawi. Household prevalence of malaria and indoor Anopheles density were quantified in two cross-sectional studies in 2016 and 2017 (5,829 residents of 1,091 households). Multilevel logistic regression was used to estimate the association between distance to the irrigation scheme and malaria infection and mosquito density. The prevalence of malaria infection was 50.2% (2,765/5,511) by histidine-rich protein 2-based malaria rapid diagnostic tests and 30.1% (1,626/5,403) by microscopy. Individuals residing in households within 3 km of the scheme had significantly higher prevalence of infection (adjusted odds ratio [aOR] = 1.41; 95% confidence interval [CI] 1.18, 1.68); school-aged children had the highest prevalence among age groups (aOR = 1.34; 95% CI 1.11, 1.63). Individuals who reported bed net use, and households with higher socioeconomic status and higher level of education for household head or spouse, had lower odds of malaria infection. Female Anopheles mosquitoes (2,215 total; Anopheles arabiensis, 90.5%, Anopheles funestus, 9.5%) were significantly more abundant in houses located within 1.5 km of the scheme. Proximity of human dwellings to the irrigation scheme increased malaria risk, but higher household wealth index reduced risk. Therefore, multisectoral approaches that spur economic growth while mitigating increased malaria transmission are needed for people living close to irrigated sites.