The relationship between species richness and area is one of the oldest, most recognized patterns in ecology. Here we provide empirical evidence for strong impacts of fisheries exploitation on the slope of the species-area relationship (SAR). Using comparative field surveys of fish on protected and exploited reefs in three oceans and the Mediterranean Sea, we show that exploitation consistently depresses the slope of the SAR for both power-law and exponential models. The magnitude of change appears to be proportional to fishing intensity. Results are independent of taxonomic resolution and robust across coral and rocky reefs, sampling protocols and statistical methods. Changes in species richness, relative abundance and patch occupancy all appear to contribute to this pattern. We conclude that exploitation pressure impacts the fundamental scaling of biodiversity as well as the species richness and spatial distribution patterns of reef fish. We propose that species-area curves can be sensitive indicators of community-level changes in biodiversity, and may be useful in quantifying the human imprint on reef biodiversity, and potentially elsewhere.