Conserving large carnivores that live in close proximity to people depends on a variety of socio-economic, political and biological factors. These include local tolerance toward potentially dangerous animals, efficacy of human carnivore conflict mitigation schemes, and identifying and then addressing the underlying causes of conflict. The Leuser Ecosystem is the largest contiguous forest habitat for the critically endangered Sumatran tiger. Its extensive forest edge is abutted by farming communities and we predict that spatial variation in human–tiger conflict (HTC) would be a function of habitat conversion, livestock abundance, and poaching of tiger and its wild prey. To investigate which of these potential drivers of conflict, as well as other biophysical factors, best explain the observed patterns, we used resource selection function (RSF) technique to develop a predictive spatially explicit model of HTC. From 148 conflict incidences recorded from 2008 to 2018 across the Leuser Ecosystem, the areas that were closer to villages and with lower occurrence of wild prey were most susceptible to tiger attacks. From 18 districts monitored, 6 stood out for having disproportionately high levels of HTC. We recommend that these areas be prioritized with increased support from conflict mitigation teams to prevent further injuries to people, livestock or tigers; district governments address one underlying cause of HTC by supporting improved animal husbandry practices, such as tiger-proof livestock pen construction; and, an increase in ranger patrol effort to recover wild prey populations. This type of priority setting approach has wide application for better determining the required management response to reduce conflicts between people and large carnivores in both tropical and temporal landscapes.