In the context of climate change in West Africa characterized by a reduction of precipitation, this study was conducted to evaluate the impact of climate change on water resources from now to the end of the 21st century in the transboundary watershed of the Sassandra River shared by Guinea and Côte d’Ivoire. Historical and future climate (Representative Concentration Pathways or RCPs 4.5 and 8.5 scenarios) data were projected with the model. The Abdus Salam ICTP RegCM4 was used. The hydrological modeling of the river basin was carried out with the conceptual hydrological model, GR2M. This model is a monthly time steps model that allows the assessment of the discharge of the Sassandra River for each climate scenario according to the 2030 (2021–2040), 2050 (2041–2060), 2070 (2061–2080), and 2090 (2081–2100) horizons. The results showed a reduction of the annual discharge when compared to the baseline (1961–1980). For the RCP 4.5, the observed values went from –1.2% in 2030 to –2.3% in 2070 and rose to –2.1% in 2090. Concerning the RCP 8.5, we saw a variation from –4.2% to –7.9% in the 2030 and 2090 horizons, respectively. With the general decrease of rainfall in West Africa, it is appropriate to assess the impact on water resources on the largest rivers (Niger, Gambia, and Senegal) that irrigate the Sahelo-Saharian zone.