Mixed pollution due to heavy metals (HMs), especially cadmium (Cd), lead (Pb), and arsenic (As), seriously endangers the safety of food produced in paddy soil. In the field experiments, foliar application of 2,3-dimercaptosuccinic acid (DMSA) at the flowering stage was found to significantly reduce the levels of Cd, Pb, total As, and inorganic As (iAs) in rice grains by 47.95%, 61.76%, 36.37%, and 51.24%, respectively, without affecting the concentration of metallonutrients, including Mn, K, Mg, Ca, Fe, and Zn. DMSA treatment significantly reduced the concentrations of Cd, Pb, and As in the panicle node, panicle neck, and rachis, while those in the flag leaves were significantly increased by up to 20.87%, 49.40%, and 32.67%, respectively. DMSA application promoted the transport of HM from roots and lower stalks to flag leaves with a maximum increase of 34.55%, 52.65%, and 46.94%, respectively, whereas inhibited the transport of HM from flag leaves to panicle, rachis, and grains. Therefore, foliar application of DMSA reduced Cd, Pb, and As accumulation in rice grains by immobilizing HMs in flag leaves. Thus, this strategy could act as a promising agronomic measure for the remediation of mixed HM contamination in paddy fields.