The understanding of climate change impacts and the associated climate extreme events at regional and local scales is of critical importance for planning and development of feasible adaptation strategies. In this paper, we present an analysis of climate change and extreme climate events in the Lake Victoria region of Tanzania, focusing on the Kagera and Geita regions. We use daily simulated climate variables (rainfall and minimum and maximum temperatures) from the Coordinated Regional Climate Downscaling Experiment Program Regional Climate Models (CORDEX_RCMs) for the analysis. Extreme climate event, rainfall, and minimum and maximum temperatures time series during historical (1971–2000) climate condition are compared to future climate projection (2011–2100) under two Representative Concentration Pathway (RCP): RCP 4.5 and RCP 8.5 emission scenarios. The existence, magnitude, and statistical significance of potential trends in climate data time series are estimated using the Mann–Kendall (MK) non-parametric test and Theil-SEN slope estimator methods. Results show that during historical (1971–2000) climate, the Lake Victoria region of Tanzania experienced a statistically significant increasing trend in temperature. The annual minimum and maximum temperatures in the Kagera and Geita regions have increased by 0.54–0.69°C, and 0.51–0.69°C, respectively. The numbers of warm days (TX90p) and warm nights (TN90p) during the historical climate have increased, while the numbers of cold days (TX10p) and cold nights (TN10p) have decreased significantly. However, in future climate condition (2011–2100) under both RCP 4.5 and RCP 8.5 emission scenarios, the Lake Victoria region is likely to experience increased temperatures and rainfall. The frequency of cold events (cold days and cold nights) is likely to decrease, while the frequency of warm events (warm days and warm nights) is likely to increase significantly. The number of consecutive wet days, the intensity of very wet days, and the number of extreme wet days are likely to increase. These results indicate that in future climate condition, socioeconomic livelihoods of people in the Kagera and Geita regions are likely to experience significant challenges from climate-related stresses. It is, therefore, recommended that appropriate planning and effective adaptation policies are in place for disaster risk prevention.