Arsenic (As) exposure is a major public health threat linked to increased risk of cancers, heart disease, diabetes, and other disorders. Ingestion of rice is the major exposure route of As for most people in the world, yet is relatively understudied in agricultural environments. The impacts of As exposure from rice consumption are particularly acute in South and Southeast Asia, where rice is a dietary staple widely cultivated in flooded paddy fields using As-contaminated groundwater, and where the combination of soil conditions and rice variety can lead to highly-impacted rice grain yields. Previous research has linked areas low in soil Zn to high levels of crop As, suggesting Zn may help to reduce arsenic uptake by rice plants. However, research has not directly evaluated the conditions that favor As incorporation into the rice plant and rice grain and have yet to explore the effect of zinc treatment on arsenic incorporation and speciation, a key variable affecting its toxicity. In this study, we will evaluate the effects of zinc oxide (ZnO) treatment on a high-yielding variety of rice grown under two different irrigation regimes—flooded and aerobic—to elucidate which conditions favor As incorporation into the rice plant and into the rice grain. Our results will be particularly important in developing agricultural management strategies aimed at ameliorating the effects of Zn deficiency and mitigating As toxicity in rice cultivation.