Ecuador's Galapagos Islands and their unique biodiversity are a global conservation priority. Here we quantify widespread plastic contamination of the marine ecosystem and design a systematic risk scoring analysis to identify the most vulnerable species. We report contamination of seafloor sediments, surface seawater, beaches, marine invertebrates and algae. Beach aspect was identified as the most significant predictor of pollution with highest accumulation on the eastern coast indicating major input of plastic waste to Galapagos from the Humboldt Current, signalling to continental and maritime sources. Local littering and waste management leakages accounted for just 2% of plastic items, highlighting the need for a regional approach to mitigation. We identify priority species for further investigation including pinnipeds, seabirds, turtles, sharks and corals due to risk of entanglement and ingestion. Finally, we recommend a monitoring and management framework for marine plastic pollution in remote oceanic islands.