Agriculture in Africa is rapidly expanding but with this comes potential disbenefits for the environment and human health. Here, we retrospectively assess whether childhood malaria in sub-Saharan Africa varies across differing agricultural land uses after controlling for socio-economic and environmental confounders. Using a multi-model inference hierarchical modelling framework, we found that rainfed cropland was associated with increased malaria in rural (OR 1.10, CI 1.03 – 1.18) but not urban areas, while irrigated or post flooding cropland was associated with malaria in urban (OR 1.09, CI 1.00 – 1.18) but not rural areas. In contrast, although malaria was associated with complete forest cover (OR 1.35, CI 1.24 – 1.47), the presence of natural vegetation in agricultural lands potentially reduces the odds of malaria depending on rural-urban context. In contrast, no associations with malaria were observed for natural vegetation interspersed with cropland (veg-dominant mosaic). Agricultural expansion through rainfed or irrigated cropland may increase childhood malaria in rural or urban contexts in sub-Saharan Africa but retaining some natural vegetation within croplands could help mitigate this risk and provide environmental co-benefits.