Arsenic (As) accumulation in rice grains threatens the health of over 150 million people in the world. Although management options including alternative wetting and drying or upland rice farming are effective approaches to reduce As uptake and accumulation, rice yield penalty is a big concern. Continuous flooding enhances rice production that is crucial for a growing global population, but enhances As bioavailability. The dilemma requires new insights and transformative approaches to control the As speciation and uptake in rice paddies. An emerging trend in the U.S. water bodies is the gradually increasing nitrate and perchlorate levels. Both chemicals are strong oxidants which can potentially oxidize As in the absence of molecular oxygen (e.g. under flooded irrigation) and consequently alter As speciation. We conducted a greenhouse study including three treatments with addition of nitrate only (10 mg/L NaNO₃), perchlorate only (50 µg/L NaClO₄), or mixed nitrate and perchlorate (10 mg/L NaNO₃+ 50 µg/L NaClO₄) as well as one control treatment (no nitrate and perchlorate) throughout the life cycle of rice. The results showed that the presence of nitrate or perchlorate increased the rice grain yield compared to the control treatment, although larger standard deviation was observed in the perchlorate treatment (six replicates). The mixed nitrate and perchlorate treatment also increased the rice grain yield, but the increase was more moderate. The total As was lower in all treatments with nitrate and/or perchlorate compared with the control, with the perchlorate alone treatment caused most reduction. As speciation analysis in plant tissues suggested that the altered As uptake was caused by the modified As speciation by the co-existing oxidizing agents. Organic As was dominant As species in rice grains, especially di-methylarsinic acid (DMA), accounting 66-76% of total As, while inorganic As was predominant in rice straws and roots in all the treatments. In summary, the presence of nitrate and perchlortae in irrigation water significantly decreased the As uptake and accumulation while enhancing the rice yield, which indicates the application of continuous flooding with oxidizing compounds as a sustainable As management strategy.