ABSTRACT: Humpback whale Megaptera novaeangliae populations have exhibited higher local abundance in parts of the Gulf of Maine in recent years, a region that is heavily impacted by both climate change and other anthropogenic effects. The Gulf of Maine is one of the most rapidly warming ecosystems in the ocean, and humpback whales use the region to feed, suggesting that there may be interactions between humpback whales, climate, and prey species in this region. We sought to understand how humpback whale densities and distributions are changing in this area in the context of prey and the environment, focusing on a particular conservation area with ample survey coverage, the Great South Channel Habitat Management Area. We used data from 16 yr of overlapping humpback whale, fish, and invertebrate surveys to relate changing humpback whale densities to environmental covariates as well as fish and invertebrate biomass. We found that humpback whale densities are increasing in the Great South Channel faster than in the surrounding area, and these increases are related to increasing biomass of squid, small gadids, and crabs and lobsters; warming temperatures; and decreasing salinity. Sand lance and herring, 2 common humpback whale prey species, decreased in this area during the study period. These interactions between humpback whales, temperature, and fish and invertebrate species could signify that increases in humpback densities are related to both biotic and abiotic variables and suggests that this conservation area may be effective at promoting the biomass of a variety of trophic levels.