Understanding of hydro-climatic variability is very crucial in water resource management, predictive planning, agricultural water management and flood risk management. In water scarce regions, hydro-climatic variability has huge impact on the available water quality and quantity. Both hydrological and climate extremes have become more problematic due to changes in anthropogenic activities and climate variability. Long-term variability in the hydro-climatic variables can affect the overall spatial, and temporal distribution of surface water. Thus, it is important to comprehend the variation in observed hydro-climatic variables on seasonal and annual time scales plus the associated effect on the hydrology and water resources. This research aimed to understand the spatial-temporal variability of hydro-climatic variables (precipitation, temperature, and streamflow) and its implication on the water resource management in the Lake Kyoga Basin (LKB), Uganda. Different hydro-climatic indices (SPI-3, Rx5, Rx95, AI, Q95 and SSI-3) were selected from the main variables (precipitation, temperature, and streamflow). A combination of different statistical techniques (Hurst, Modified Mann-Kendell and wavelet coherence) were employed to assess the trend, variability, and their interaction among the selected hydro-climatic indices. The interaction of the different variables plus their effect on water resource management were evaluated using wavelet coherent statistical approach. The results obtained from this study are an indication of climate variability in the LKB, exhibiting extremes events of both drought and floods. Both extremes have an impact on the river flows as floods can be associated with soil erosion, land slides among others and prolonged droughts with water and food scarcity. In most parts of the LKB precipitation is decreasing while aridity is increasing. The decreasing precipitation in LKB has been attributed to the climatic teleconnection which might imply that the teleconnections have a cause in the variations of the hydro-climatic indices