It’s unequivocal that the global climate is changing, including the rise in atmospheric temperature and variability in amount and pattern of precipitation, and the rate of temperature change in the Himalayan region is higher than the global average. Since precipitation and temperature are the major driving factors of water resources in the Himalayas both upstream and downstream regions, it is important to understand theimpacts of climate change in water resource availability in the future. In this study, we analyzed the historical hydro-climate data and developed a suitable ensemble of the Coordinated Regional Downscaling Experiment (CORDEX) climate models for the Karnali River Basin (KRB) in western Nepal and assessed the future water availability in different climate scenarios using a semi-distributed catchment scale hydrological model the Soil and Water Assessment Tool (SWAT). The climate data analysis shows that the atmospheric temperature is rising throughout the basin but there is high spatial variability in precipitation trend. The historical river discharge data analysis do not show any significant trend, however, there is some inter-annual variability. Future projection shows that the annual precipitation amount will increase compared to the baseline so does the river discharge. However, this increase is not uniform for all seasons. The post-monsoon season having the lowest observed precipitation will get lesser amount of precipitation in the future and the river discharge also follows the same trend. These anomalies play a crucial role in determining the future water availability for agriculture, hydropower, ecosystem functioning and its services availability to the people living in the KRB as well as in the downstream region.