The increase in flood events observed in West African countries, and often in specific river basins, can be influenced by several factors, including anthropogenic land use and land-cover changes. However, the potential contribution of land cover changes to flood events still needs to be explored, especially in West Africa. Here, the fully coupled atmosphere-hydrology WRF-Hydro system, which comprises an atmospheric model and additionally incorporates the surface, subsurface, overland flow, and channel routing, is used to investigate the potential impact of a land cover change scenario on flood events in the Senegal River basin. The simulation was performed from 2010 to 2020, with a calibration period spanning from 2011 to 2012 and a validation period from 2013 to 2020. Several skill scores, including Nash-Sutcliffe Efficiency (NSE), BIAS, and Kling-Gupta Efficiency (KGE), were utilized to assess the calibration and validation performances. Additionally, two planetary boundary layer schemes (PBL5 and PBL7) were used to determine their associated uncertainty. Our results show that the best calibration results (NSE = 0.70; KGE = 0.83; PBIAS = −7% and BE = 0.67) in the Senegal River basin are obtained with PBL5 when the calibration is performed with a SLOPE parameter 0.03. A similar good performance was also obtained for the validation with NSE = 0.74, KGE = 0.84, and PBIAS = −8%. Likewise, our findings indicate that converting savanna to woody savannas can elevate water resources, with a 2% rise in precipitation and a 4% increase in runoff. This transition also correlates with an increase in moderate flood events (3500–4000 m3/s), a decrease in severe floods (4000–5000 m3/s), and their associated occurrence of extreme floods (>5000 m3/s) in the Senegal River basin.