AbstractAbove‐permissible levels of arsenic (As) in irrigation water lead to toxic levels in wheat grains, increasing health risks for humans. In this study, two zinc (Zn)‐biofortified wheat (Triticum aestivum L.) cultivars (Akbar‐2019 and Zincol‐2016) were grown in pots with two Zn application rates (0 and 8 mg Zn kg−1) and three levels of As in irrigation water (distilled‐water control, 100 and 1000 µg As L−1). Irrigation with As‐contaminated water decreased dry matter yields, concentrations of grain phosphorus (P) and Zn, and estimated daily intake (EDI) of Zn. Conversely, it increased grain As concentration and As EDI. Soil Zn application mitigated the negative effects of As on dry matter yields of both cultivars while simultaneously enhancing grain Zn concentration and Zn EDI. On average, Zn application increased grain Zn concentration by 114% compared to no Zn application. Additionally, Zn application decreased grain As concentration at all As levels. In conclusion, this study suggests that applying Zn to Zn‐biofortified wheat irrigated with As‐contaminated water can mitigate the toxic effects of As on wheat. It increase Zn concentration and decrease As concentration in wheat grains, which is vital for enhancing grain quality for human consumption.