Global climate change has local implications. Focusing on datasets from the topographically-challenging Karnali river basin in Western Nepal, this research provides an overview of hydro-climatic parameters that have been observed during 1981–2012. The spatial and temporal variability of temperature and precipitation were analyzed in the basin considering the seven available climate stations and 20 precipitation stations distributed in the basin. The non-parametric Mann–Kendall test and Sen’s method were used to study the trends in climate data. Results show that the average precipitation in the basin is heterogeneous, and more of the stations trend are decreasing. The precipitation shows decreasing trend by 4.91 mm/year, i.e., around 10% on average. Though the increasing trends were observed in both minimum and maximum temperature, maximum temperature trend is higher than the minimum temperature and the maximum temperature trend during the pre-monsoon season is significantly higher (0.08 °C/year). River discharge and precipitation observations were analyzed to understand the rainfall-runoff relationship. The peak discharge (August) is found to be a month late than the peak precipitation (July) over the basin. Although the annual precipitation in most of the stations shows a decreasing trend, there is constant river discharge during the period 1981–2010.