Our study investigated the influence of bottom-up and top-down drivers on the declining fledging success at a once thriving breeding colony of Caspian terns (Hydroprogne caspia). Situated at the mouth of the Columbia River, OR, East Sand Island (ESI) is home to the largest Caspian tern breeding colony in North America. Since 2001, the decline in fledging success of Caspian terns at ESI has been associated with a significant increase in average river discharge during May and June. During the years 2001–2011, the abundance of forage fish available to terns in the estuary was inversely related to river discharge. This relationship also apparently affected the reliance of nest predators on the tern colony as a food source, resulting in increased disturbance and decreased fledging success at the tern colony in years of higher river discharge. There was a significant longitudinal increase in disturbance rates by bald eagles (Haliaeetus leucocephalus) during June for terns nesting at the ESI colony, and eagle disturbance rates were positively associated with May river discharge. We also found a significant increase in kleptoparasitism rates of terns by hybrid glaucous-winged/western gulls (Larus glaucescens x Larus occidentalis) since 2001, and Caspian tern fledging success at ESI decreased with increasing average annual rates of gull kleptoparasitism. Our results support the hypothesis that the decline in Caspian tern fledging success at this large estuarine colony was primarily driven by the interaction of bottom-up and top-down factors, influencing tern fledging success through the food supply and triggering potential predators to identify the tern breeding colony as an alternative source of prey.