Geographically isolated wetlands (GIWs) are characterized as ‘isolated’ because they are embedded by uplands, though they potentially exhibit a gradient of hydrologic, biological, or chemical connections to other surface waters. In fact, recent field studies have begun to elucidate that GIWs exhibit varying degrees of hydrologic connectivity. In this study, we examine the influence of GIWs on streamflow, a potential indicator of GIW hydrologic connectivity with surface waters. We assess annual and seasonal spatially based statistical relationships between GIW characteristics (e.g. volume and extent) and streamflow across a dense network of subbasins using a hybrid modeling approach. Our method involves the Spatial Stream Network (SSN) model, which considers spatial autocorrelation of model covariates explicitly, and the Soil and Water Assessment Tool (SWAT), which predicts streamflow across a network of 579 subbasins in the lower Neuse River Basin, North Carolina, USA. Our study results suggest that GIWs, to some extent, influence streamflow. The further GIWs are from a stream, the greater their capacity to increase streamflow due to the physiographic setting, hypothesized transit times, and sequencing of watershed hydrologic connectivity in the study area. However, as the combined extent of GIWs and non‐GIWs increases in subbasins, seasonal and annual streamflow decreases. Results also suggest that other landscape indicators of watershed‐scale hydrology can, in aggregate with GIWs and non‐GIWs, explain variations in seasonal and annual simulated streamflow. Our study findings begin to elucidate the aggregate influence of GIWs on streamflow, providing insights for future decision‐making on GIW protection and management. Copyright © 2015 John Wiley & Sons, Ltd.