Reef-building corals are highly sensitive to rising ocean temperatures, and substantial adaptation will be required to persist in changing ocean conditions. In this study, we focused on the potential for adaptation in Orbicella faveolata, a dominant reef-builder in the Caribbean. We conducted thermal stress experiments using corals collected from natural populations in Bocal del Toro, Panama. We estimated the heritability of variation in bleaching responses, conducted a genome-wide association study to examine the functional basis of the variation, and profiled gene expression in contrasting phenotypes.