Understanding the response of Himalayan-Karakoram (HK) rivers to climate change is crucial for ~1 billion people who partly depend on these water resources. Policy-makers tasked with sustainable water resources management require an assessment of the rivers’ current status and potential future changes. We show that glacier and snow melt are important components of HK rivers, with greater hydrological importance for the Indus basin than for the Ganges and Brahmaputra basins. Total river runoff, glacier melt, and seasonality of flow are projected to increase until the 2050s, with some exceptions and large uncertainties. Critical knowledge gaps severely affect modeled contributions of different runoff components, future runoff volumes, and seasonality. Therefore, comprehensive field observation–based and remote sensing–based methods and models are needed.