Weathering processes in orogenic belts play a pivotal role in Earth's climate regulation. However, the link between silicate weathering and hydroclimatic fluctuations remains elusive. Here, we investigate the lithium‑neodymium isotopic compositions (δ7Li, εNd) and clay mineralogy of sediments in the northeastern Bay of Bengal to determine if the δ7Li can be used as a reliable tracer of the chemical weathering intensity and to assess how weathering responses to hydroclimate changes. δ7Li and εNd values range from −2.4 ‰ to 0.4 ‰ and − 12.5 to −8.9, respectively, with clay mineralogy dominated by illite (57 % on average). A decline in δ7Li since 13.5 ka, averaging −1.3 ‰, compared to −0.7 ‰ between 25 ka and 13.5 ka, indicates intensified weathering aligned with monsoon variations. Prominent millennial-scale δ7Li fluctuations (2.8 ‰ in maximum) during the last deglaciation, showing lower values during the cold events (Younger Drys and Heinrich stadial 1), imply a different mechanism of weathering response to hydroclimate changes. Shift of high mountain- versus floodplain-dominated weathering regimes and hydrology induced changes in water-rock interaction time or water residence time, are suggested to be responsible for δ7Li changes at glacial-interglacial scale and millennial scale, respectively. Our study provides key evidence for weathering response to short-term climate change, and highlights the carbon sink role of silicate weathering in floodplains at short-term scales and the potential of Li isotopes in reconstructing past hydroclimate changes.