Throughout the tropics, hunting and fishing are critical livelihood activities for many Indigenous peoples. However, these practices may not be sustainable following recent socio-economic changes in Indigenous populations. To understand how human population growth and increased market integration affect hunting and fishing patterns, we conducted semi-structured interviews in five Kukama-Kukamilla communities living along the boundary of the Pacaya-Samiria National Reserve, in the Peruvian Amazon. Extrapolated annual harvest rates of fish and game species by these communities amounted to 1,740 t and 4,275 individuals (67 t), respectively. At least 23 fish and 27 game species were harvested. We found a positive correlation between village size and annual community-level harvest rates of fish and a negative relationship between market exposure and mean per-capita harvest rates of fish. Catch-per-unit-effort (CPUE) analyses indicated local depletion of fish populations around larger, more commercial communities. Catch-per-unit-effort of fish was lower in more commercial communities and fishers from the largest village travelled further into the Reserve, where CPUE was higher. We found no effect of village size or market exposure on harvest rates or CPUE of game species. However, larger, more commercial communities targeted larger, economically valuable species. This study provides evidence that human population growth and market-driven hunting and fishing pose a growing threat to wildlife and Indigenous livelihoods through increased harvest rates and selective harvesting of species vulnerable to exploitation.