The Mekong River is an important transboundary water resource for a large part of southeast Asia. Here, we reconstruct the flow of the Mekong River in its upper and lower basin over the last three centuries using tree-ring chronologies from southeast Asia. Apparently extreme low flow events, like those that occurred in 2010, are not exceptional over the length of the reconstruction. Flow varies on interannual to decadal time scales and shows a recent increase in the lower basin, both of which have implications for future sustainable development in the watershed.