On 22 March 2021, a ~50 M m3 ice-rock avalanche occurred from 6500 m asl in the Sedongpu basin, southeastern Tibet. The avalanche transformed into a highly mobile flow which temporarily blocked the Yarlung Tsangpo river. The avalanche flow lasted ~5 minutes and produced substantial geomorphological reworking. This event, and previous ones from the basin, occurred concurrently with, or shortly after recorded positive air temperature anomalies. The occurrence of future large mass flows from the basin cannot be ruled out, and their impacts must be carefully considered given implications for sustainable hydropower and associated socioeconomic development in the region.