Small-scale fisheries are major contributors to global fishing catch and to the livelihoods of many coastal communities. However, little is known about these fisheries, the spatial heterogeneity in which they are found, and the factors that explain this heterogeneity. In Chile, the distinct environmental regimes driven by the Humboldt Current System can contribute to a high diversity in the species targeted by small-scale fisheries. Through a Chilean case-study, we aimed to characterize how environmental and socio-economic conditions influence small-scale benthic fisheries in 15 coves, straddling two biogeographic regions along 24 degrees of latitude (ca. 2600 km) and administered by a nation-wide management framework. We compiled and analyzed a long-term database generated by a standardized monitoring protocol in order to determine how fishing techniques, benthic resource diversity, effort and fishers’ income vary along the coastline. Our results highlighted that small-scale fisheries are strongly influenced by the variations in the environmental conditions, which determine variations in landings along the coast. Our analyses also illustrated how fishers seek to ensure their livelihoods by dealing with regional and local environmental conditions, ecology of marine resources, socio-economic context and a management system that is not able to accommodate fisheries’ heterogeneity. Our results suggest that future changes to the Chilean management system should integrate the spatial variation observed among small-scale fisheries to ensure sustainable livelihoods of the fishers and conservation of the marine resources. Fishery management rules should be shaped according to the region where they are applied, moving from homogeneous nation-wide systems, or systems adapted from administrative divisions to differentiated co-management systems based on biogeographic units.