The Nasia catchment is the reservoir for significant surface water resources in Northern Ghana and home to numerous subsistence farmers engaged in rainfed and dry season irrigation farming. Yet there is little understanding of the hydro-climatic and land use /cover conditions of this basin. We analyzed 50 years of minimum (Tmin) and maximum temperature (Tmax), wind speed (WS), sunshine duration(S), Rainfall(R), relative humidity (RH), discharge (D) and potential evapotranspiration (PET) data, 15 years of remotely sensed normalized difference vegetation index (NDVI) data and 30 years of land use/cover image data. Results show that Tmin, Tmax, WS, and PET have increased significantly (P < 0.05). RH and S significantly declined. R, D and NDVI have insignificantly decreased (P > 0.05). A significant abrupt change in almost all hydroclimatic variables started in the 1980s, a period that coincides with the occurrence of drought events in the region except WS in 2001, R in 1968 and D in 1975. Also, D showed a positive significant correlation with RH, R and PET, but insignificant positive relationship with S. D also showed negative insignificant correlation with Tmin, Tmax and WS. Areas covered with shrubland and settlement/bare lands have increased to the disadvantage of cropland, forest, grassland and water bodies. We conclude that climate change impact is quite noticeable in the basin; indicating water scarcity and possibilities of droughts. The analysis performed herein is a vital foundation for further studies to simulate and predict the effect of climate change on the water resources, agriculture and livelihood in the Nasia basin.