Human activities are changing ecosystems at an unprecedented rate, yet large-scale studies into how local human impacts alter natural systems and interact with other aspects of global change are still lacking. Here we provide empirical evidence that local human impacts fundamentally alter relationships between ecological communities and environmental drivers. Using tropical coral reefs as a study system, we investigated the influence of contrasting levels of local human impact using a spatially extensive dataset spanning 62 outer reefs around inhabited Pacific islands. We tested how local human impacts (low versus high determined using a threshold of 25 people km−2 reef) affected benthic community (i) structure, and (ii) relationships with environmental predictors using pre-defined models and model selection tools. Data on reef depth, benthic assemblages, and herbivorous fish communities were collected from field surveys. Additional data on thermal stress, storm exposure, and market gravity (a function of human population size and reef accessibility) were extracted from public repositories. Findings revealed that reefs subject to high local human impact were characterised by relatively more turf algae (>10% higher mean absolute coverage) and lower live coral cover (9% less mean absolute coverage) than reefs subject to low local human impact, but had similar macroalgal cover and coral morphological composition. Models based on spatio-physical predictors were significantly more accurate in explaining the variation of benthic assemblages at sites with low (mean adjusted-R2 = 0.35) rather than high local human impact, where relationships became much weaker (mean adjusted-R2 = 0.10). Model selection procedures also identified a distinct shift in the relative importance of different herbivorous fish functional groups in explaining benthic communities depending on the local human impact level. These results demonstrate that local human impacts alter natural systems and indicate that projecting climate change impacts may be particularly challenging at reefs close to higher human populations, where dependency and pressure on ecosystem services are highest.