Unsustainable exploitation of natural resources is increasingly affecting the highly biodiverse tropics [1, 2]. Although rapid developments in remote sensing technology have permitted more precise estimates of land-cover change over large spatial scales [3–5], our knowledge about the effects of these changes on wildlife is much more sparse [6, 7]. Here we use field survey data, predictive density distribution modeling, and remote sensing to investigate the impact of resource use and land-use changes on the density distribution of Bornean orangutans (Pongo pygmaeus). Our models indicate that between 1999 and 2015, half of the orangutan population was affected by logging, deforestation, or industrialized plantations. Although land clearance caused the most dramatic rates of decline, it accounted for only a small proportion of the total loss. A much larger number of orangutans were lost in selectively logged and primary forests, where rates of decline were less precipitous, but where far more orangutans are found. This suggests that further drivers, independent of land-use change, contribute to orangutan loss. This finding is consistent with studies reporting hunting as a major cause in orangutan decline [8–10]. Our predictions of orangutan abundance loss across Borneo suggest that the population decreased by more than 100,000 individuals, corroborating recent estimates of decline . Practical solutions to prevent future orangutan decline can only be realized by addressing its complex causes in a holistic manner across political and societal sectors, such as in land-use planning, resource exploitation, infrastructure development, and education, and by increasing long-term sustainability . Video Abstract: [Figure presented] Voigt et al. show the negative impact of natural resource use on the density distribution of Bornean orangutans. The habitat of half of the population was affected. Over 16 years, more than 100,000 individuals were lost. Decline rates were highest when habitat was removed. Absolute losses were largest in selectively logged and primary forests.