Some of the largest and most erosive floods on Earth result from the failure of glacial dams. While potentially cataclysmic ice dams are recognized to have repeatedly formed along ice-sheet margins, much less is known about the frequency and longevity of ice dams caused by mountain glaciers, and their impact on landscape evolution. Here we present field observations and results from cosmogenic nuclide dating that allow reconstructing a >100-k.y.-long history of glacial damming in the Shyok Valley, eastern Karakoram (South Asia). Our field observations provide evidence that Asia’s second-longest glacier, the Siachen, once extended for over 180 km and blocked the Shyok River during the penultimate glacial period, leading to upstream deposition of a more than 400-m-thick fluvio-lacustrine valley fill. 10Be-depth profile modeling indicates that glacial damming ended with the onset of the Eemian interglacial and that the Shyok River subsequently incised the valley fill at an average rate of ∼4–7 m k.y.–1. Comparison with contemporary ice-dammed lakes in the Karakoram and elsewhere suggests recurring outburst floods during the aggradation period, while over 25 cycles of fining-upward lake deposits within the valley fill indicate impounding of floods from farther upstream. Despite prolonged damming, the net effect of this and probably earlier damming episodes by the Siachen Glacier is dominated by glacial erosion in excess of fluvial incision, as evidenced by a pronounced overdeepening that follows the glaciated valley reach. Strikingly similar overdeepened valleys at all major confluences of the Shyok and Indus Rivers with Karakoram tributaries indicate that glacial dams and subsequent outburst floods have been widespread and frequent in this region during the Quaternary. Our study suggests that the interaction of Karakoram glaciers with the Shyok and Indus Rivers promoted valley incision and headward erosion into the western margin of the Tibetan Plateau.