Climate change is one of the biggest challenges facing development and continuation of sustainable aquaculture in temperate regions. We primarily consider the ecological and physical resilience of aquaculture in the Gulf of Maine (GoM), where a thriving industry includes marine algae, extensive and intensive shellfish aquaculture, and a well-established Atlantic salmon industry, as well as the infrastructure required to support these economically important ventures. The historical record of sea surface temperature in the GoM, estimated from gridded, interpolated in situ measurements, shows considerable interannual and decade-scale variability superimposed on an overall warming trend. Climate model projections of sea surface temperature indicate that the surface waters in the GoM could warm 0.5-3.5°C beyond recent values by the year 2100. This suggests that, while variability will continue, anomalous warmth of marine heatwaves that have been observed in the past decade could become the norm in the GoM ca. 2050, but with the most significant impacts to existing aquaculture along the southernmost region of the coast. We consider adaptations leading to aquacultural resilience despite the effects of warming, larger numbers of harmful nonindigenous species (including pathogens and parasites), acidification, sea-level rise, and more frequent storms and storm surges. Some new species will be needed, but immediate attention to adapt existing species (e.g. preserve/define wild biodiversity, breed for temperature tolerance and incorporate greater husbandry) and aquaculture infrastructure can be successful. We predict that these measures and continued collaboration between industry, stakeholders, government and researchers will lead to sustaining a vibrant working waterfront in the GoM.