High-Mountain Asia exhibits one of the highest increases in vegetation greenness on Earth, subsequently influencing the exchange of water and energy between the land surface and the atmosphere. Given the strong interactions between the hydrosphere, the biosphere, and the cryosphere, understanding the drivers of greening in this highly complex region with significant land cover heterogeneity is essential to assess the changes in the regional water budget. Here, we perform a holistic multivariate remote sensing analysis to simultaneously examine the primary components of the terrestrial water cycle from 2003 to 2020 and decipher the principal drivers of greening in High-Mountain Asia. We identified three drivers of greening: (1) precipitation drives greening in mid and low elevation areas covered by evergreen and mixed forests (e.g., Irrawaddy basin), (2) decreases in snow enhance greening in most of the hydrologic basins, and (3) irrigation induces greening in irrigated lands (Ganges–Brahmaputra and Indus).