On the climate-health issue, studies have already attempted to understand the influence of climate change on the transmission of malaria. Extreme weather events such as floods, droughts, or heat waves can alter the course and distribution of malaria. This study aims to understand the impact of future climate change on malaria transmission using, for the first time in Senegal, the ICTP’s community-based vector-borne disease model, TRIeste (VECTRI). This biological model is a dynamic mathematical model for the study of malaria transmission that considers the impact of climate and population variability. A new approach for VECTRI input parameters was also used. A bias correction technique, the cumulative distribution function transform (CDF-t) method, was applied to climate simulations to remove systematic biases in the Coupled Model Intercomparison Project Phase 5 (CMIP5) global climate models (GCMs) that could alter impact predictions. Beforehand, we use reference data for validation such as CPC global unified gauge-based analysis of daily precipitation (CPC for Climate Prediction Center), ERA5-land reanalysis, Climate Hazards InfraRed Precipitation with Station data (CHIRPS), and African Rainfall Climatology 2.0 (ARC2). The results were analyzed for two CMIP5 scenarios for the different time periods: assessment: 1983–2005; near future: 2006–2028; medium term: 2030–2052; and far future: 2077–2099). The validation results show that the models reproduce the annual cycle well. Except for the IPSL-CM5B model, which gives a peak in August, all the other models (ACCESS1–3, CanESM2, CSIRO, CMCC-CM, CMCC-CMS, CNRM-CM5, GFDL-CM3, GFDL-ESM2G, GFDL-ESM2M, inmcm4, and IPSL-CM5B) agree with the validation data on a maximum peak in September with a period of strong transmission in August–October. With spatial variation, the CMIP5 model simulations show more of a difference in the number of malaria cases between the south and the north. Malaria transmission is much higher in the south than in the north. However, the results predicted by the models on the occurrence of malaria by 2100 show differences between the RCP8.5 scenario, considered a high emission scenario, and the RCP4.5 scenario, considered an intermediate mitigation scenario. The CanESM2, CMCC-CM, CMCC-CMS, inmcm4, and IPSL-CM5B models predict decreases with the RCP4.5 scenario. However, ACCESS1–3, CSIRO, NRCM-CM5, GFDL-CM3, GFDL-ESM2G, and GFDL-ESM2M predict increases in malaria under all scenarios (RCP4.5 and RCP8.5). The projected decrease in malaria in the future with these models is much more visible in the RCP8.5 scenario. The results of this study are of paramount importance in the climate-health field. These results will assist in decision-making and will allow for the establishment of preventive surveillance systems for local climate-sensitive diseases, including malaria, in the targeted regions of Senegal.