The water resources of the Chari River basin, contributing more than 90% of the water to one of the largest lakes in Africa, known as Lake Chad, are highly vulnerable to natural and anthropogenic changes. Therefore, the changes in water resources were predicted for the next 20 years (i.e., 2016–35) by using the harmonic regression model (HRM), one of the most sophisticated time series methods, and also projected under representative concentration pathways (RCPs) by using the multimodel approach for the periods 2021–50, 2051–80, and 2081–2100, with respect to the baseline period (1971–2001). The Tropical Rainfall Measuring Mission (TRMM), Climatic Research Unit (CRU), and dynamically downscaled climatic data were used in the analysis of the present study. The results showed that under MME-RCP2.6 (multimodel ensemble of RCMs), low flow (average of low-flow months, December–July), high flow (August–November), and annual flow were projected to decrease in the future. In contrast, under MME-RCP4.5 and MME-RCP8.5, high and annual flows were projected to increase in all three time horizons, while low flow will decrease except in 2021–50 under MME-RCP8.5. In the next two decades, the HRM showed decrease in all type of flows (low, high, and annual), very similar to the results under MME-RCP2.6 for the same period. In contrast, almost all flows are expected to increase under MME-RCP4.5 and MME-RCP8.5 in the next two decades. On the whole, the flows are expected to decrease under the HRM and RCP2.6 but to increase under RCP4.5 and RCP8.5.