The Kobuk River runs west along the southern Brooks Range from Gates of the Arctic National Park in Alaska, USA, to the Chukchi Sea. It is highly vulnerable to changes in climate due to its sub-Arctic location, unique geography, and permafrost foundation. Combined with its pristine condition, these qualities make the Kobuk an ideal system upon which to build a conceptual model for predicting ecosystem effects of climate change. We constructed a conceptual ecosystem model for the Kobuk River synthesizing surveyed baseline hydrologic, geomorphic and biotic conditions with literature on Arctic rivers. While the mainstem Kobuk has limited biological productivity, it provides spawning habitat and connectivity for large resident and migratory fish that rely upon off-channel habitat for food resources. System function is dependent largely on intermittent pulse flows that connect riverine habitats, allowing periods of late summer high productivity in off-channel habitat. Spring break-up and hill slope processes are critically important for maintaining habitat complexity and inter-connectivity. Climate change models predict the region will experience a disproportionate increase in average winter air temperature relative to summer temperatures, in the number of ice-free days, and in annual rainfall. Our conceptual model predicts that changes to fish and invertebrate populations on the Kobuk River will result not from physiological responses to increased temperatures, but rather to shifts in two main physical drivers: 1) spring break-up intensity, resulting in changes to scour rate and sediment deposition; and 2) discontinuous permafrost melt, resulting in widespread heterogeneous zones of active layer thickening and thermokarsting. The interaction of these two drivers offers four potential scenarios of geomorphic change in the system and four dramatically different biological outcomes. This model should help managers and scientists evaluate the magnitude and direction of ecosystem changes as they occur within the Kobuk system and potentially other sub-Arctic river systems.