Cadmium (Cd) and arsenic (As) that accumulate in rice grains can enter the human body via ingestion, posing a human health threat. Chelated iron (Fe) fertilizer application is an effective strategy for reducing Cd and As concentrations in grains; however, its mechanism of action is unknown. We investigated effects of ethylenediamine tetraacetic acid disodium ferrous (EDTA center dot Na2Fe) at Fe application rates of 0, 25, 50, and 75 mg kg-1 on Cd and As availability in soil and accumulation in rice grains. EDTA center dot Na2Fe significantly reduced soil Cd-As availability and significantly decreased CaCl2-Cd and KH2PO4-As concentrations by 27.8-39.2 % and 17.7-28.4 %, respectively. EDTA center dot Na2Fe facilitated Fe plaque (IP) formation and increased Cd (CdIP) and As (AsIP) sequestration in IP; furthermore, FeIP, CdIP, and AsIP increased significantly by 70.7-125 %, 109-150 %, and 88.1-168 %, respectively. In roots, EDTA center dot Na2Fe reduced the Cd concentration (CdR) but increased the As concentration (AsR). EDTA center dot Na2Fe reduced the Cd (CdG) and As (AsG) concentrations in grains by 29.8-46.2 % and 18.5-33.3 %, respectively. The optimal simultaneous reduction effect of CdG and AsG was observed at an EDTA center dot Na2Fe application rate of 50 mg kg-1 Fe. The results indicated that CdG was mainly affected by Cd availability, translocation factor (TF) CdR/CdIP, and TF CdG/CdR, and AsG was mainly affected by TF AsG/AsR, followed by TF AsR/AsIP and AsIP. In summary, EDTA center dot Na2Fe reduced CdG and AsG by reducing Cd and As availability in soil, improving Cd and As sequestration in IP, and reducing Cd transport from IP to roots and As transport from roots to grain. Moderate application of EDTA center dot Na2Fe effectively reduced CdG and AsG in Cd-As- contaminated paddy soil.