Sensitivity of reef-building corals to environmental factors has far-reaching ecosystem implications, especially in the limited number of cold-water coral (CWC) species that form reefs in the deep sea. Understanding CWC responses to large-scale oceanographic variation in their natural habitat can elucidate their sensitivity to global anthropogenic stressors. Here, we use skeletal samples to analyse fine-scale phenotypic variation in the widespread reef-building CWC Desmophyllum pertusum (Lophelia pertusa) in relation to broad physicochemical gradients in different sites across the Atlantic Ocean and Mediterranean Sea. We find evidence, amidst local and regional differentiation, of species-wide growth responses to physicochemical factors, mainly affecting corallite length, width and their ratio (slenderness). Our results suggest that higher temperature and lower oxygen levels negatively affect skeletal linear extension and budding rate of polyps. As also hinted by the reduced corallite length and slenderness in less developed reefs, these widespread responses may lead to a general decline in CWC reef growth rates as a long-term consequence of ocean warming and deoxygenation. Given this relevance, such responses can be used to model reef growth in a changing ocean.