West Africa serves as a critical region for the co-circulation of mosquito-borne flaviviruses, which often precipitate sporadic outbreaks. This study investigated the seropositivity to dengue virus serotypes 1-4 (DENV-1-4), Zika virus (ZIKV), yellow fever virus (YFV), and West Nile virus (WNV) in three regions of Senegal: Sindia, Thies, and Kedougou. We retrospectively analyzed 470 serum samples for flavivirus immunoglobulin G (IgG) using a DENV-2 envelope (E) ELISA. Our findings revealed an overall flavivirus seroprevalence of 37.23%. Among the DENV-2 E IgG positive samples, the proportion of subjects with IgG to DENV-1-4, ZIKV, YFV, or WNV NS1 was 57.14%, 12.57%, 80.57%, and 17.14%, respectively, with 66.86% harboring neutralizing antibodies against two or more flaviviruses. We also identified that residents in Sindia (ZIKV, aOR, 9.428; 95% CI: 1.882-47.223 and WNV, aOR, 6.039; 95% CI: 1.855-19.658) and Kedougou (ZIKV, aOR, 7.487; 95% CI: 1.658-33.808 and WNV, aOR, 1.142; 95% CI: 0.412-3.164) were at significant risk for ZIKV and WNV exposure. This study underscores the complexity of flavivirus epidemiology in West Africa and the necessity for enhanced surveillance to inform public health strategies.