On 22 March 2021, an approximately 50 Mm3 ice-rock avalanche occurred from 6500 m a.s.l. in the Sedongpu basin, southeastern Tibet. The avalanche transformed into a highly mobile mass flow which temporarily blocked the Yarlung Tsangpo river. The avalanche flow lasted ∼ 5 min and produced substantial geomorphological reworking. This event, and previous ones from the basin, occurred concurrently with, or shortly after, positive seasonal 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.