Human impacts can homogenize and simplify ecosystems, favoring communities that are no longer naturally coupled with (or reflective of) the background environmental regimes in which they are found. Such a process of biophysical decoupling has been explored little in the marine environment due to a lack of replication across the intact-to-degraded ecosystem spectrum. Coral reefs lacking local human impacts provide critical baseline scenarios in which to explore natural biophysical relationships, and provide a template against which to test for their human-induced decoupling. Using 39 Pacific islands, 24 unpopulated (relatively free from local human impacts) and 15 populated (with local human impacts present), spanning 45° of latitude and 65° of longitude, we ask, what are ‘natural’ biophysical relationships on coral reefs and do we see evidence for their human-induced decoupling? Estimates of the percent cover of benthic groups were related to multiple physical environmental drivers (sea surface temperature, irradiance, chlorophyll-a, and wave energy) using mixed-effects models and island mean condition as the unit of replication. Models across unpopulated islands had high explanatory power, identifying key physical environmental drivers of variations in benthic cover in the absence of local human impacts. These same models performed poorly and lost explanatory power when fitted anew to populated (human impacted) islands; biophysical decoupling was clearly evident. Furthermore, key biophysical relationships at populated islands (i.e. those relationships driving benthic variation across space in conjunction with chronic human impact) bore little resemblance to the baseline scenarios identified from unpopulated islands. Our results highlight the ability of local human impacts to decouple biophysical relationships in the marine environment and fundamentally restructure the natural rules of nature.