Two centuries of multiple human impacts and successive changes in a North Atlantic food web

European colonization of North America, severely altered terrestrial and aquatic ecosystems alike. Here, we integrate archaeological, historical, and recent data to derive the ecological history of the Quoddy Region, Bay of Fundy, Canada, an upwelling region rich in marine diversity and productivity. We document successive changes on all trophic levels from primary producers to top predators over the last centuries. Our objectives were to (1) construct a baseline of what was natural in the coastal ocean, and (2) analyze the sequence and potential interaction of multiple human impacts. Archaeological records highlight the abundance and diversity of marine species used by indigenous people over the last 2000-3000 years. Europeans colonized the area in the late 1700s and rapidly transformed the environment by multiple top-down (exploitation), bottom-up (nutrient loading), and side-in (habitat destruction, pollution) impacts. Most large vertebrates were severely overexploited by 1900, leading to the extinction of three mammal and six bird species. Diadromous fish dramatically declined after river damming in the early 1800s, and recovery was prevented by subsequent river pollution. Overfishing of groundfish stocks started in the late 1800s, gradually leading to a final collapse in the 1970s. In the 20th century, decline of traditional fisheries induced a shift to low trophic level harvesting and aquaculture, which increased exponentially over the past 20 years. Eutrophication caused shifts in seaweed and phytoplankton communities: Some long-lived rockweeds were replaced by annual bloom-forming algae, and diatoms were replaced by dinoflagellates. Today, the once unique Quoddy Region shows the most common signs of degradation found in highly impacted coastal areas worldwide. Multiple human influences have altered abundance and composition of every trophic level in the food web and reduced upper trophic levels by at least one order of magnitude. We highlight cumulative and indirect effects that impair the ability to predict and manage highly impacted coastal ecosystems. On the other hand, simple protection and restoration measures in the 20th century led to the recovery of some species. It is these successes that provide guidance for a more sustainable interaction of humans with their marine environment.