The contamination of arsenic (As) in agricultural soil and groundwater poses a serious threat to both plants and human health worldwide. Wheat, being a predominant staple food crop, is considered a major source of carcinogenic threats due to As. The present study aimed to investigate the effect of a foliar spray of thiourea (TU; 500 mg L−1) on As accumulation in various parts of the plant, growth, and yield of wheat plants grown in contaminated field (soil As: 18.90 mg kg−1). Exogenous application of TU resulted in a significant decrease in As accumulation in grains (54% lower in comparison to control). The decrease in grain As reduced hazard quotient (HQ) and incremental lifetime cancer risk (ILCR) to safe levels. TU supplementation also improved the average grain yield by 30%. The shoot and root MDA concentrations were decreased by 26 and 60%, respectively at 75 d on TU supplementation. The activity of various antioxidant enzymes (superoxide dismutase, ascorbate peroxidase, guaiacol peroxidase, catalase, and glutathione reductase) in general depicted significant decline or no significant change denoting amelioration of As stress upon supply of TU. In conclusion, TU supplementation decreased As load in the wheat grains and enhanced the productivity of the crop by ameliorating As stress. The strategy of TU supplementation may find field application after evaluation of the strategy in several wheat varieties and in different environmental conditions.