<p>The flow regime of the largest lake in Southeast Asia, Tonle Sap Lake, is driven by the reverse flow phenomenon caused by its link with the Mekong River. This reverse flow makes the lake one of the most productive aquatic ecosystems globally and thus provides important economic opportunities for local communities. The recent human activities in the upstream, as well as climate variations, have resulted in unforeseen alterations in the flow regime of the Mekong River and Tonle Sap Lake. However, little is known about the explicit attribution of different parts of the upstream basin to these variations, which would be essential for transboundary water management. To unveil these attributions, we developed a novel modeling setup consisting of hydrodynamic, hydrological, and machine learning models. This modeling setup allowed us to separate the impacts of a) climate variation, b) human activities in the Chinese part of the basin, and b) the lower part of the basin (i.e., Laos, Thailand, and Vietnam). During the 2001–2009 baseline, when human modifications to the flow were still minimal, we found that Tonle Sap Lake received, on average, 42.4 km<sup>3</sup>/yr water from the Mekong, 48.2 % of the total inflow to the lake. During the period of increased human activities, 2010–2020, this decreased due to climate variation to 40.1 km<sup>3</sup>/yr (a 5.7 % drop), which was further exacerbated by the increased human activities in the upstream parts of the basin (China ~ 7.3%, Laos, Thailand, and Vietnam ~ 9 %). Additionally, during the flow period when water flows from the lake towards the Mekong, on average, 31 % of the total inflow into the Mekong Delta originated from the lake during the baseline period. Climate variation decreased this by 4 percentage points (pp), i.e., to 27 %, while the human activities in China and lower parts of the basin decreased this by 1.6 pp (25.4 %) and 1.9 pp (25.1 %), respectively. Our findings unveiled the attributions of different drivers on Tonle Sap Lake’s hydrology and will facilitate transboundary water management in the basin. The impacts of future plans on different parts of the basin should be carefully evaluated together with existing anthropogenic impacts, as well as climate change, to minimize the further impacts on the lake and Mekong River.</p>

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