Fishing pressure on coral reef ecosystems has been frequently linked to reductions of large fishes and reef fish biomass. Associated impacts on overall community structure are, however, less clear. In size-structured aquatic ecosystems, fishing impacts are commonly quantified using size spectra, which describe the distribution of individual body sizes within a community. We examined the size spectra of coral reef fish communities at 38 US-affiliated Pacific islands, spanning from near pristine to highly human populated. Reef fish community size spectra slopes ‘steepened’ steadily with increasing human population and proximity to market due to a reduction in the relative biomass of large fishes and an increase in the dominance of small fishes. In contrast, total fish community biomass was substantially lower on inhabited islands than uninhabited ones, regardless of human population density. Comparing the relationship between size spectra and reef fish biomass, we found that on populated islands size spectra steepened linearly with declining biomass, whereas on uninhabited islands size spectra and biomass were unrelated. Size spectra slopes also were steeper in regions of low sea surface temperature but were insensitive to variation in other environmental and geomorphic covariates. In contrast, reef fish biomass was highly sensitive to biophysical conditions, being influenced by oceanic productivity, sea surface temperature, island type, and habitat complexity. Our results suggest that community size structure is more robust than total fish biomass to increasing human presence and that size spectra are reliable indicators of exploitation impacts across regions of different fish community compositions, environmental drivers, and fisheries types. Size-based approaches that link directly to functional properties of fish communities, and are relatively insensitive to abiotic variation across biogeographic regions, offer great potential for developing our understanding of fishing impacts in coral reef ecosystems.