The aim of the research was to investigate the effects of climate variability on selected water bodies in the Upper East Region of Ghana using time series decomposition and simple linear regression analyses. Data on temperature and rainfall (1960–2015), annual total fish catch (1996–2016), and the recorded water levels (1987–2015) of a major reservoir, the Tono, were used. Time series decomposition analyses were performed on the rainfall, temperature, and water level data to identify their trends. While temperature was increasing, rainfall was decreasing and resulted in a decrease in the water level in the Tono Reservoir. The decreasing water level in the reservoir made fish catch easier, which led to overfishing. Out of the other 39 dugouts studied, 8 (21%) were silted. Also, rainfall was decreasing at 4.4% per decade and minimum and maximum temperatures were increasing at 2.5% and 0.03% per decade, respectively. The minimum, maximum, and mean water levels of the Tono Reservoir were 3.7, 8.0, and 4.9 meters (m), respectively. The water level of the Tono Reservoir was decreasing by −0.08 m per year. It is concluded that the water level in the Tono Reservoir was continually decreasing as a result of decreasing rainfall and increasing maximum and minimum temperatures. To maintain a much more stable microclimate and decrease the siltation rate of the reservoirs, farmers are advised to stop farming along the banks of water bodies and avoid clearing vegetation. Fishermen are also encouraged to adopt fish farming in enclosed areas within the reservoir to meet the growing protein demands in the Upper East Region of Ghana.