Droughts have been a major factor leading to the Tri-State Water Wars in the southeastern United States. One of the primary issues related to the conflict is the reduction in baseflow levels in the Flint River during droughts. This affects the availability of freshwater resources to support the endangered mussel species in the Flint and Apalachicola Rivers and threatens the shellfish industry in the Apalachicola Bay. Study of large-scale climate phenomena as well as the interactions of interannual with decadal and multidecadal oceanic–atmospheric phenomena can provide valuable information regarding regional climatic conditions such as droughts and their impact on water resources. This study was conducted to quantify the impacts of climate variability cycles on baseflow levels in the Flint River. The individual and coupled impacts of the El Nino-Southern Oscillation (ENSO), Pacific Decadal Oscillation (PDO), Atlantic Multidecadal Oscillation (AMO), and North Atlantic Oscillation (NAO) on baseflow were quantified. The non-parametric Joint Rank Fit (JRFit) procedure was used to provide a robust test of the significance of interactions between the phases of ENSO–PDO, ENSO–AMO and ENSO–NAO baseflows. Simple-main effect comparisons were also performed using the JRFit model to estimate significant difference between the positive and negative phase baseflows of PDO, AMO and NAO associated with El Nino or La Nina phases. The results indicate that the phases of ENSO, AMO and NAO significantly affect baseflows in the Flint River. Interaction tests showed that the PDO and AMO phases modulate ENSO phase baseflows. La Nina associated with positive phases of PDO and AMO resulted in greater decrease in baseflow levels of approximately 28% and 33%, respectively. However, La Nina associated with negative phase of AMO showed above normal baseflows. The results illustrate the importance of coupled analyses of climate variability by providing a better understanding of the severity of droughts and their impact on baseflows. The results obtained from this study can be used by water managers in the region as a guide for the issuance of drought severity-based water restrictions.