Due to climate and environmental changes, sub-Saharan Africa (SSA) has experienced several drought and flood events in recent decades with serious consequences on the economy of the sub-region. In this context, the region needs to enhance its capacity in water resources management, based on both good knowledge of contemporary variations in river flows and reliable forecasts. The objective of this article was to study the evolution of current and future (near (2022–2060) and distant (2061–2100)) flows in the So'o River Basin (SRB) in Cameroon. To achieve this, the Pettitt and modified Mann–Kendall tests were used to analyze hydrometeorological time series in the basin. The Soil and Water Assessment Tool (SWAT) model was used to simulate the future flows in the SRB. The results obtained show that for the current period, the flows of the So'o decrease due to the decrease in precipitation. For future periods, a change in precipitation in line with the predictions of the CCCma model will lead to a decrease in river discharge in the basin, except under the RCP8.5 scenario during the second period (2061–2100), where will note an increase compared to the historical period of approximately +4%. Results from the RCA4 model project an increase in precipitation which will lead to an increase in river discharge by more than +50%, regardless of the period and the scenario considered. An increase in discharges was noted in some cases despite a drop in rainfall, particularly in the case of discharges simulated for the second period (2061–2100) from the outputs of the CCCma model. This seems to be a consequence of the increase in impervious spaces, all the more the runoff increases during this period according to the model. Results from this study could be used to enhance water resources management in the basin investigated and the region.