The deep sea encompasses the largest ecosystems on Earth. Although poorly known, deep seafloor ecosystems provide services that are vitally important to the entire ocean and biosphere. Rising atmospheric greenhouse gases are bringing about significant changes in the environmental properties of the ocean realm in terms of water column oxygenation, temperature, pH and food supply, with concomitant impacts on deep-sea ecosystems. Projections suggest that abyssal (3000–6000 m) ocean temperatures could increase by 1°C over the next 84 years, while abyssal seafloor habitats under areas of deep-water formation may experience reductions in water column oxygen concentrations by as much as 0.03 mL L–1 by 2100. Bathyal depths (200–3000 m) worldwide will undergo the most significant reductions in pH in all oceans by the year 2100 (0.29 to 0.37 pH units). O2 concentrations will also decline in the bathyal NE Pacific and Southern Oceans, with losses up to 3.7% or more, especially at intermediate depths. Another important environmental parameter, the flux of particulate organic matter to the seafloor, is likely to decline significantly in most oceans, most notably in the abyssal and bathyal Indian Ocean where it is predicted to decrease by 40–55% by the end of the century. Unfortunately, how these major changes will affect deep-seafloor ecosystems is, in some cases, very poorly understood. In this paper, we provide a detailed overview of the impacts of these changing environmental parameters on deep-seafloor ecosystems that will most likely be seen by 2100 in continental margin, abyssal and polar settings. We also consider how these changes may combine with other anthropogenic stressors (e.g., fishing, mineral mining, oil and gas extraction) to further impact deep-seafloor ecosystems and discuss the possible societal implications.