Long, continuous records of Late Quaternary environmental change are rare in Southeast Asia, yet they are crucial for understanding the nature of early human dispersal and occupation in the Australasian region. We present a new record of palaeomonsoon activity extending back to 35,000 BP (years before the present), based on the analysis of oxygen isotope ratios (δ18O) in the freshwater bivalve Margaritanopsis laosensis excavated from the Tham Lod and Ban Rai rockshelters in Mae Hong Son Province, northwest Thailand. Long-term changes in the M. laosensis δ18O record reflect changes in the δ18O of the river water in which these organisms grew, and correlate well with changes in speleothem δ18O records of east Asian monsoon rainfall from Hulu Cave and Dongge Cave in China. The new northwest Thailand δ18O sequence indicates wetter and relatively unstable climatic conditions from 35,000 to 20,000 BP, followed by drier conditions from 20,000 to 11,500 BP. A period of peak aridity occurred around 15,600 BP during Heinrich Event 1, suggesting that the intertropical convergence zone shifted southward when the North Atlantic region cooled. However, there is little evidence for the Younger Dryas event at ∼12,800–11,500 BP. After 9,800 BP, precipitation increased substantially and climatic variability declined. Our findings provide an improved baseline against which to gauge interactions between early humans and climate change in Southeast Asia. For example, there was no significant change in the prehistoric flake stone technology used at Tham Lod and Ban Rai despite the bivalve δ18O evidence for substantial climate change in the region. Also, the climatic impact of the Younger Dryas event appears to have been less intense in northwest Thailand compared to the cooling and drying observed in China, and may explain why agriculture made a relatively late appearance in Thailand, possibly involving migrants from China.