Climate change is reshaping biological communities and has already generated novel ecosystems. The functioning of novel ecosystems could depart markedly from that of existing systems and therefore obscure the impacts of climate change. We illustrate this possibility for coral reefs, which are at the forefront of climatic stress. Disease has been a principal cause of reef degradation and is expected to worsen with increased future thermal stress. However, using a field-tested epizoological model, we show that high population turnover within novel ecosystems enhances coral resistance to epizootics. Thus, disease could become a less important driver of change in the future. We emphasize the need to move away from projections based on historic trends toward predictions that account for novel behavior of ecosystems under climate change.