It has been suggested that moderate to high fluoride ion concentrations in the presence of calcium in groundwater can represent human health hazards resulting in possible lesions in tubular cells, leading to chronic kidney disease of unknown etiology (CKDu). This study focuses on fluoride removal in the presence of calcium using iron oxide nanoparticles (FeONs) as an effective adsorbent in single- and multi-solute batch-studies. Fluoride and calcium removal by FeONs in single-solute batch-studies occurred only by adsorption. Both species followed the Langmuir isotherm model and pseudo second-order kinetics, indicating monolayer adsorption and chemisorption, respectively. In multi-solute batch-studies, fluoride removal was attributed to adsorption and chemical precipitation forming CaF2 in almost similar magnitude. For calcium removal in multi-solute studies, adsorption, co-precipitation, and precipitation were the prominent mechanisms, with co-precipitation dominant. Thus, FeONs are effective in fluoride removal by adsorption in both the presence and absence of calcium. FeONs could also be used successfully year-round in tropical climates, where calcium levels vary substantially, to lessen the risk of CKDu.