The formation mechanism and quality evaluation of surface water and groundwater have provided valuable information on water management of alpine catchment, such as Tibet Plateau. However, scarce knowledge of surface water and groundwater has been achieved from Eastern Himalayan syntaxis in eastern Tibet due to harsh and complicated natural and geological conditions. This study collected 60 water samples from the Layue alpine catchment within Eastern Himalayan syntaxis, including 35 samples of groundwater and 25 of surface water. A combination of multivariate statistical analysis, ion ratio analysis, geochemical modeling, hydrogen and oxygen isotope analysis, and water quality index (WQI) analysis was employed to explore hydrochemical processes and irrigation and portable suitability. Results indicate that the groundwater types identified include bicarbonate-calcium, sulfate·chlorine-sodium, and mixed bicarbonate-calcium·sodium, while surface water are sulfate·chlorine-sodium, mixed bicarbonate-calcium·sodium, and mixed chlorine-calcium·magnesium types. Groundwater recharge primarily originates from meteoric precipitation, with recharge elevations ranging from 2216 to 3698 m, while surface water receives both precipitation and groundwater recharge in a proportion of 50.51%–87.96%. Silicate weathering and carbonate dissolution predominantly control the hydrochemical compositions. Sodium adsorption ratios (0.75–88.55) and electrical conductivity (85.20–1686.12 μs/cm) indicate water resource are mostly suitable for irrigation. The entropy-weighted water quality index (97% in total <100) denotes the suitability for portable use. These achievements would provide substantial support for the sustainable water management in alpine areas, especially for Tibet Plateau.