A sequential extraction procedure (SEP), batch desorption experiments and the concept of partition coefficient were applied on seven sediment samples from the Subansiri-Dikrong-Ranganadi River System (SDRS), a subset of the upper Brahmaputra floodplain (BFP), to understand leaching of arsenic (As) and fluoride (F−). Sediment samples were collected during monsoon and post-monsoon seasons from each of three river banks to distinguish the effect of annual cyclic flooding events on As content and mobilization. SEP revealed that the readily leachable chemisorbed As phase and amorphous Fe (hydr)oxides were the principal contributors to mobilized As during the monsoon season. Constant flushing of the rivers removed most of the physisorbed and chemisorbed As during the monsoon. A submerged anoxic condition toward late monsoon resulted in Fe (hydr)oxides becoming the dominant source of removable As during the post-monsoon season. Iron in the sediments was positively correlated with F− during both monsoon and post-monsoon seasons. This suggests that Fe (hydr)oxides are a host for F− and a correlation between reductive hydrolysis and F−. Removal of Fe (hydr)oxides from the sediments significantly reduced As retention/leaching capacity. Arsenic desorption was especially high from raw sediments of the Ranganadi River owing to the fact that it had the highest amount of As associated with Fe (hydr)oxides, which falls sharply in the post-monsoon season due to a prolonged submerged state leading to reductive dissolution. However, as leached F− is being constantly flushed out by the SDRS, F− contamination may not pose a problem in the current or futuristic scenarios.